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Sample records for childhood acute lymphoblastic

  1. Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  2. Treatment Options for Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... Childhood AML Treatment Research Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Childhood Acute ... Myelogenous Leukemia Treatment Hairy Cell Leukemia Treatment Past treatment for cancer and certain genetic conditions affect the ...

  3. GLUCOCORTICOID RECEPTOR IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA

    Institute of Scientific and Technical Information of China (English)

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

    1999-01-01

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

  4. Pharmacogenetics influence treatment efficacy in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Davidsen, Marie Louise; Dalhoff, Kim; Schmiegelow, Kjeld

    2008-01-01

    in treatment resistance and toxic side effects. As most childhood acute lymphoblastic leukemia treatment protocols include up to 13 different chemotherapeutic agents, the impact of individual SNPs has been difficult to evaluate. So far focus has mainly been on the widely used glucocorticosteroids, methotrexate...

  5. Pharmacogenetics Influence Treatment Efficacy in Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Devidsen, M.L.; Dalhoff, K.; Schmiegelow, K.

    2008-01-01

    in treatment resistance and toxic side effects. As most childhood acute lymphoblastic leukemia treatment protocols include up to 13 different chemotherapeutic agents, the impact of individual SNPs has been difficult to evaluate. So far Focus has mainly been on the widely used glucocorticosteroids, methotrexate...

  6. Obesity in patients with acute lymphoblastic leukemia in childhood

    Directory of Open Access Journals (Sweden)

    Iughetti Lorenzo

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    The pattern of infections in the first years of life modulates our immune system, and a low incidence of infections has been linked to an increased risk of common childhood acute lymphoblastic leukemia (ALL). We here present a new interpretation of these observations--the adrenal hypothesis......--that proposes that the risk of childhood ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis that increase plasma cortisol levels. This may directly eliminate leukemic cells as well as preleukemic cells for the ALL subsets...

  8. High-Risk Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

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

    2009-01-01

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

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

    Science.gov (United States)

    2016-10-24

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

  10. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    DEFF Research Database (Denmark)

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

    2016-01-01

    .001) if relapse occurred in the period 1992-2001. Factors independently predicting mortality after relapse included short duration of first remission, bone marrow involvement, age ten years or over, unfavorable cytogenetics, and Down syndrome. T-cell immunophenotype was not an independent prognostic factor unless......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...... included in the study. There were no statistically significant differences in outcome between the up-front protocols or between the relapse protocols used, but an improvement over time was observed. The 5-year overall survival for patients relapsing in the period 2002-2011 was 57.5±3.4%, but 44.7±3.2% (P

  11. Osteogenic toxicity in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet)

    2013-01-01

    textabstractBone mineral density (BMD) Our multi-center study in children treated according to the Dutch Childhood Oncology Group (DCOG)-ALL9 protocol showed a three-years cumulative incidence of fractures of 18%. BMD of ALL patients was lower than of healthy peers. The year after treatment disconti

  12. Impaired dexamethasone-related increase of anticoagulants is associated with the development of osteonecrosis in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet); I.M. Appel (Inge); R. Pieters (Rob); M.M. van den Heuvel-Eibrink (Marry)

    2008-01-01

    textabstractCoagulation alterations may be involved in osteonecrosis in childhood acute lymphoblastic leukemia. Retrospectively, we evaluated the available coagulation parameters at diagnosis and during induction treatment of 161 acute lymphoblastic leukemia patients: 24 with symptomatic osteonecros

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

    Science.gov (United States)

    Pui, Ching-Hon; Evans, William E.

    2013-01-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Science.gov (United States)

    2016-08-25

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    PURPOSE: Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. PATIENTS AND METHODS: We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980...... and 2007. RESULTS: Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival...... estimates for AML were 11.2% ± 2.9% for 125 patients diagnosed before 2000 and 34.1% ± 6.3% for 61 patients diagnosed after 2000 (P survival estimates for MDS were 17.1% ± 6.4% (n = 36) and 48.2% ± 10.6% (n = 33; P = .005). Allogeneic stem-cell transplantation failed to improve outcome...

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

    Science.gov (United States)

    2014-03-20

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

  18. Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-01-22

    Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  19. Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Nielsen, Stine N; Frandsen, Thomas L;

    2014-01-01

    The antileukemic mechanisms of 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy are poorly understood, but the benefits of several years of myelosuppressive maintenance therapy for acute lymphoblastic leukemia are well proven. Currently, there is no international consensus on drug...... intensive and toxic earlier treatment phases, and often more challenging. Ongoing research address the applicability of drug metabolite measurements for dose adjustments, extensive host genome profiling to understand diversity in treatment efficacy and toxicity, and alternative thiopurine dosing regimens...

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

    Science.gov (United States)

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

    2013-01-01

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

  1. Sleep, fatigue, depression, and quality of life in survivors of childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Huisman, J.; Bierings, M.B.; Hoogerbrugge, P.M.; Kaspers, G.J.L.

    2013-01-01

    BACKGROUND: With the improved survival of childhood acute lymphoblastic leukemia (ALL), the effect of treatment on psychosocial well-being becomes increasingly relevant. Literature on sleep and fatigue during treatment is emerging. However, information on these subjects after treatment is sparse. Th

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Prognostic impact of peripheral blood white blood cell count (WBC) at the diagnosis of childhood acute lymphoblastic leukaemia (ALL) was evaluated in a population-based consecutive series of 2666 children aged 1-15 treated for ALL between 1992 and 2008 in the five Nordic countries (Denmark, Finland...

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

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit

    2016-01-01

    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......, 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...

  4. Childhood acute lymphoblastic leukemia and indicators of early immune stimulation: a Childhood Leukemia International Consortium study.

    Science.gov (United States)

    Rudant, Jérémie; Lightfoot, Tracy; Urayama, Kevin Y; Petridou, Eleni; Dockerty, John D; Magnani, Corrado; Milne, Elizabeth; Spector, Logan G; Ashton, Lesley J; Dessypris, Nikolaos; Kang, Alice Y; Miller, Margaret; Rondelli, Roberto; Simpson, Jill; Stiakaki, Eftichia; Orsi, Laurent; Roman, Eve; Metayer, Catherine; Infante-Rivard, Claire; Clavel, Jacqueline

    2015-04-15

    The associations between childhood acute lymphoblastic leukemia (ALL) and several proxies of early stimulation of the immune system, that is, day-care center attendance, birth order, maternally reported common infections in infancy, and breastfeeding, were investigated by using data from 11 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980-2010). The sample included 7,399 ALL cases and 11,181 controls aged 2-14 years. The data were collected by questionnaires administered to the parents. Pooled odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Day-care center attendance in the first year of life was associated with a reduced risk of ALL (odds ratio = 0.77, 95% confidence interval: 0.71, 0.84), with a marked inverse trend with earlier age at start (P < 0.0001). An inverse association was also observed with breastfeeding duration of 6 months or more (odds ratio = 0.86, 95% confidence interval: 0.79, 0.94). No significant relationship with a history of common infections in infancy was observed even though the odds ratio was less than 1 for more than 3 infections. The findings of this large pooled analysis reinforce the hypothesis that day-care center attendance in infancy and prolonged breastfeeding are associated with a decreased risk of ALL.

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

    Science.gov (United States)

    Vrooman, Lynda M; Silverman, Lewis B

    2016-10-01

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

  6. Outcomes after Induction Failure in Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

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

    2012-01-01

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

  7. Diffusion tensor imaging and neurocognition in survivors of childhood acute lymphoblastic leukaemia.

    Science.gov (United States)

    Edelmann, Michelle N; Krull, Kevin R; Liu, Wei; Glass, John O; Ji, Qing; Ogg, Robert J; Sabin, Noah D; Srivastava, Deo Kumar; Robison, Leslie L; Hudson, Melissa M; Reddick, Wilburn E

    2014-11-01

    Survivors of childhood acute lymphoblastic leukaemia are at risk for neurocognitive impairment, though little information is available on its association with brain integrity, particularly for survivors treated without cranial radiation therapy. This study compares neurocognitive function and brain morphology in long-term adult survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy alone (n = 36) to those treated with cranial radiation therapy (n = 39) and to healthy control subjects (n = 23). Mean (standard deviation) age at evaluation was 24.9 (3.6) years for the chemotherapy group and 26.7 (3.4) years for the cranial radiation therapy group, while time since diagnosis was 15.0 (1.7) and 23.9 (3.1) years, respectively. Brain grey and white matter volume and diffusion tensor imaging was compared between survivor groups and to 23 healthy controls with a mean (standard deviation) age of 23.1 (2.6) years. Survivors treated with chemotherapy alone had higher fractional anisotropy in fibre tracts within the left (P < 0.05), but not in the right, hemisphere when compared to controls. Survivors of acute lymphoblastic leukaemia, regardless of treatment, had a lower ratio of white matter to intracranial volume in frontal and temporal lobes (P < 0.05) compared with control subjects. Survivors of acute lymphoblastic leukaemia treated with chemotherapy alone performed worse in processing speed (P < 0.001), verbal selective reminding (P = 0.01), and academics (P < 0.05) compared to population norms and performed better than survivors treated with cranial radiation therapy on verbal selective reminding (P = 0.02), processing speed (P = 0.05) and memory span (P = 0.009). There were significant associations between neurocognitive performance and brain imaging, particularly for frontal and temporal white and grey matter volume. Survivors of acute lymphoblastic leukaemia treated with chemotherapy alone demonstrated significant long-term differences in

  8. Cure rates of childhood acute lymphoblastic leukemia in Lithuania and the benefit of joining international treatment protocol

    DEFF Research Database (Denmark)

    Vaitkevičienė, Goda; Matuzevičienė, Rėda; Stoškus, Mindaugas

    2014-01-01

    BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) represents the largest group of pediatric malignancies with long-term survival rates of more than 80% achieved in developed countries. Epidemiological data and survival rates of childhood ALL in Lithuania were lacking. Therefore, the aim of...

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

    DEFF Research Database (Denmark)

    Borst, Louise; Wesolowska, Agata; Joshi, Tejal;

    2012-01-01

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

  10. Dust metal loadings and the risk of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Whitehead, Todd P; Ward, Mary H; Colt, Joanne S; Dahl, Gary; Ducore, Jonathan; Reinier, Kyndaron; Gunier, Robert B; Katharine Hammond, S; Rappaport, Stephen M; Metayer, Catherine

    2015-01-01

    We evaluated the relationship between the risk of childhood acute lymphoblastic leukemia (ALL) and the levels of metals in carpet dust. A dust sample was collected from the homes of 142 ALL cases and 187 controls participating in the California Childhood Leukemia Study using a high volume small surface sampler (2001-2006). Samples were analyzed using microwave-assisted acid digestion in combination with inductively coupled plasma mass spectrometry for arsenic, cadmium, chromium, copper, lead, nickel, tin, tungsten, and zinc. Eight metals were detected in at least 85% of the case and control homes; tungsten was detected in nickel: 0.95 (0.82, 1.09), tin: 0.96 (0.86, 1.08), and zinc: 0.94 (0.84, 1.05)). Our findings do not support the hypothesis that metals in carpet dust are risk factors for childhood ALL.

  11. Challenges in implementing individualized medicine illustrated by antimetabolite therapy of childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Nersting, Jacob; Borst, Louise; Schmiegelow, Kjeld

    2011-01-01

    of acceptable toxicity, an individualized therapeutic approach is indicated. The mapping of the human genome and technological developments in DNA sequencing, gene expression profiling, and proteomics have raised the expectations for implementing genotype-phenotype data into the clinical decision process...... illustrated by studies involving childhood acute lymphoblastic leukemia (ALL), where each patient may receive up to 13 different anticancer agents over a period of 2-3 years. The challenges include i) addressing important, but low-frequency outcomes, ii) difficulties in interpreting the impact of single drug...

  12. Brain volume and cognitive function in adult survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Edelmann, Michelle N; Krull, Kevin R

    2013-10-01

    The survival rate for childhood acute lymphoblastic leukemia (ALL) is greater than 80%. However, many of these survivors develop long-term chronic health conditions, with a relatively common late effect being neurocognitive dysfunction. Although neurocognitive impairments have decreased in frequency and severity as treatment has evolved, there is a subset of survivors in the current treatment era that are especially vulnerable to the neurotoxic effects of ALL and its treatment. Additionally, little is known about long-term brain development as survivors mature into adulthood. A recent study by Zeller et al. compared neurocognitive function and brain volume in 130 adult survivors of childhood ALL to 130 healthy adults matched on age and sex. They identified the caudate as particularly sensitive to the neurotoxic effects of chemotherapy. We discuss the implications and limitations of this study, including how their findings support the concept of individual vulnerability to ALL and its treatment.

  13. The impact of CYP3A5*3 on risk and prognosis in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Borst, Louise; Wallerek, Sandra; Dalhoff, Kim Peder;

    2011-01-01

    Objectives:  Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood; however, little is known of the molecular etiology and environmental exposures causing the disease. Cytochrome P450 3A5 (CYP3A5) plays a crucial role in the catalytic oxidation of endogenous metabolites and to...

  14. Influence of functional polymorphisms of the MDR1 gene on vincristine pharmacokinetics in childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Plasschaert, S.L.A.; Groninger, E.; Boezen, M.; Kema, I.P.; Vries, E.G.F. de; Uges, D.R.A.; Veerman, A.J.P.; Kamps, W.A.; Vellenga, E.; Graaf, S.S.N. de; Bont, E.S. de

    2004-01-01

    OBJECTIVE: Our objective was to investigate the effect of single nucleotide polymorphisms (SNPs) in the P-glycoprotein MDR1 gene on vincristine pharmacokinetics and side effects in childhood acute lymphoblastic leukemia. METHODS: From 52 of 70 children who participated in a previous study on vincris

  15. Paternal Smoking and Risk of Childhood Acute Lymphoblastic Leukemia: Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Ruiling Liu

    2011-01-01

    Full Text Available Objective. To investigate the association between paternal smoking and childhood acute lymphoblastic leukemia (ALL. Method. We identified 18 published epidemiologic studies that reported data on both paternal smoking and childhood ALL risk. We performed a meta-analysis and analyzed dose-response relationships on ALL risk for smoking during preconception, during pregnancy, after birth, and ever smoking. Results. The summary odds ratio (OR of childhood ALL associated with paternal smoking was 1.11 (95% Confidence Interval (CI: 1.05–1.18, I2=18% during any time period, 1.25 (95% CI: 1.08–1.46, I2=53% preconception; 1.24 (95% CI: 1.07–1.43, I2=54% during pregnancy, and 1.24 (95% CI: 0.96–1.60, I2=64% after birth, with a dose-response relationship between childhood ALL and paternal smoking preconception or after birth. Conclusion. The evidence supports a positive association between childhood ALL and paternal ever smoking and at each exposure time period examined. Future epidemiologic studies should assess paternal smoking during well-defined exposure windows and should include biomarkers to assess smoking exposure and toxicological mechanisms.

  16. Implications of infectious diseases and the adrenal hypothesis for the etiology of childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    F. Azevedo-Silva

    2010-03-01

    Full Text Available Acute leukemia is the most frequent cancer in children. Recently, a new hypothesis was proposed for the pathogenesis of childhood acute lymphoblastic leukemia (ALL. The so-called "adrenal hypothesis" emphasized the role of endogenous cortisol in the etiology of B-cell precursor ALL. The incidence peak of ALL in children between 3 to 5 years of age has been well documented and is consistent with this view. The adrenal hypothesis proposes that the risk of childhood B-cell precursor ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis. It suggests that the increased plasma cortisol levels would be sufficient to eliminate all clonal leukemic cells originating during fetal life. Because Brazil is a continental and tropical country, the exposure to infections is diversified with endemic viral and regionally non-viral infections, with some characteristics that support the recent adrenal hypothesis. Here we discuss this new hypothesis in terms of data from epidemiological studies and the possible implications of the diversity of infections occurring in Brazilian children.

  17. TFDP3 confers chemoresistance in minimal residual disease within childhood T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    Chu, Ming; Yin, Kailin; Dong, Yujun; Wang, Pingzhang; Xue, Yun; Zhou, Peng; Wang, Yuqi; Wang, Yuedan

    2017-01-01

    Acquired drug resistance in childhood T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. In this study, a novel gene therapy target for childhood T-ALL to overcome chemoresistance was discovered: TFDP3 increased in the minimal residual disease (MRD) positive childhood T-ALL patients. Then, we established a preclinical model of resistance to induction therapy to examine the functional relevance of TFDP3 to chemoresistance in MRD derived from Jurkat/E6-1. Jurkat xenografts in NOD/SCID mice were exposed to a four drug combination (VXLD) of vincristine (VCR), dexamethasone (DEX), L-asparaginase (L-asp) and daunorubicin (DNR). During the 4-week VXLD treatment, the level of TFDP3 increased 4-fold. High expression of TFDP3 was identified in the re-emerging lines (Jurkat/MRD) with increased chemoresistance, which is correlated with partially promoter demethylation of TFDP3. Downregulation of TFDP3 by RNA interference reversed chemoresistance in Jurkat/MRD accompanied by reinstated E2F1 activity that coincided with increased levels of p53, p73, and associated proapoptotic target genes. Importantly, TFDP3 silencing in vivo induced apparent benefit to overcome chemoresistance in combination with VXLD treatment. Collectively, TFDP3 confers chemoresistance in MRD within childhood T-ALL, indicating that TFDP3 is a potential gene therapy target for residual cancer. PMID:27902457

  18. Chemotherapy with cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP) in childhood acute lymphoblastic leukemia (ALL).

    Science.gov (United States)

    Sallan, S E; Camitta, B M; Chan, D M; Traggis, D; Jaffe, N

    1977-01-01

    Three groups of children with acute lymphoblastic leukemia (ALL) were treated with intermittent cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP). Group A (no prior relapse) and Group B (prior single-agent relapse) received COAP after 12 months on another chemotherapy regimen. Children in Group C (prior relapse on multiagent regimens) received COAP following A-COAP (asparaginase plus COAP) reinduction. Median disease-free survival after beginning COAP was not reached for Group A, but was only 7 months for Groups B and C. As of November 1976, there were 8 of 15 Group A patients, 1 of 12 Group B patients, and 1 of 28 Group C patients who had remained disease-free from 38 to 60 (median 54.5) months and were off chemotherapy. COAP has activity in childhood ALL. However, effectiveness is markedly diminished in patients with prior bone marrow relapse.

  19. Using adaptive model predictive control to customize maintenance therapy chemotherapeutic dosing for childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Noble, Sarah L; Sherer, Eric; Hannemann, Robert E; Ramkrishna, Doraiswami; Vik, Terry; Rundell, Ann E

    2010-06-07

    Acute lymphoblastic leukemia (ALL) is a common childhood cancer in which nearly one-quarter of patients experience a disease relapse. However, it has been shown that individualizing therapy for childhood ALL patients by adjusting doses based on the blood concentration of active drug metabolite could significantly improve treatment outcome. An adaptive model predictive control (MPC) strategy is presented in which maintenance therapy for childhood ALL is personalized using routine patient measurements of red blood cell mean corpuscular volume as a surrogate for the active drug metabolite concentration. A clinically relevant mathematical model is developed and used to describe the patient response to the chemotherapeutic drug 6-mercaptopurine, with some model parameters being patient-specific. During the course of treatment, the patient-specific parameters are adaptively identified using recurrent complete blood count measurements, which sufficiently constrain the patient parameter uncertainty to support customized adjustments of the drug dose. While this work represents only a first step toward a quantitative tool for clinical use, the simulated treatment results indicate that the proposed mathematical model and adaptive MPC approach could serve as valuable resources to the oncologist toward creating a personalized treatment strategy that is both safe and effective.

  20. Poor adherence to dietary guidelines among adult survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Robien, Kim; Ness, Kirsten K; Klesges, Lisa M; Baker, K Scott; Gurney, James G

    2008-11-01

    Recent studies indicate that survivors of childhood acute lymphoblastic leukemia (ALL) are at increased risk of obesity and cardiovascular disease, conditions that healthy dietary patterns may help ameliorate or prevent. To evaluate the usual dietary intake of adult survivors of childhood ALL, food frequency questionnaire data were collected from 72 participants, and compared with the 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention recommendations, the Dietary Approaches to Stop Hypertension (DASH) diet, and the 2005 United States Department of Agriculture (USDA) Food Guide. Mean daily energy intake was consistent with estimated requirements; however, mean body mass index was 27.1 kg/m2 (overweight). Dietary index scores averaged fewer than half the possible number of points on all 3 scales, indicating poor adherence to recommended guidelines. No study participant reported complete adherence to any set of guidelines. Although half the participants met minimal daily goals for 5 servings of fruits and vegetables (WCRF/AICR recommendations) and Food Guide), participants reported dietary sodium and added sugar intake considerably in excess of recommendations, and suboptimal consumption of whole grains. Guideline adherence was not associated with either body mass index or waist circumference, perhaps due to the low dietary index scores. These findings suggest that dietary intake for many adult survivors of childhood ALL is not concordant with dietary recommendations that may help reduce their risk of obesity, cardiovascular disease, or other treatment-related late effects.

  1. Health-related quality of life assessment in Indonesian childhood acute lymphoblastic leukemia

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    Sutaryo

    2008-11-01

    Full Text Available Abstract Background Most studies on Health-related Quality of Life (HRQOL in children with cancer were conducted in developed countries. The aims of this study were to assess the HRQOL in childhood acute lymphoblastic leukemia (ALL patients in Indonesia and to assess the influence of demographic and medical characteristics on HRQOL. Methods After cultural linguistic validation, a cross-sectional study of HRQOL was conducted with childhood ALL patients and their guardians in various phases of treatment using the Pediatric Quality of Life Inventory™ (PedsQL™ 4.0 Generic Core Scale and the Pediatric Quality of Life Inventory™ (PedsQL™ 3.0 Cancer Module. Results Ninety-eight guardians and 55 patients participated. The internal consistency of both scales ranged from 0.57 to 0.92. HRQOL of Indonesian patients was comparable with those in developed countries. There were moderate to good correlations between self-reports and proxy-reports, however guardians tended to report worse HRQOL than patients. Children of the 2–5 year-group significantly had more problems in procedural anxiety, treatment anxiety and communication subscales than in older groups (p Conclusion Younger children had more problems in procedural anxiety, treatment anxiety and communication subscales. Therefore, special care during intervention procedures is needed to promote their normal development. Psychosocial support should be provided to children and their parents to facilitate their coping with disease and its treatment.

  2. Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Gregers, J; Gréen, H; Christensen, I J;

    2015-01-01

    The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those...... and prednisolone induction therapy was more prominent in patients with 3435TT variant versus 3435CT/3435CC (P=0.01/P

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

    OpenAIRE

    Aberuyi, N; Rahgozar, S; Moafi, A

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is one of the most prevalent hematologic malignancies in children. Although the cure rate of ALL has improved over the past decades, the most important reason for ALL treatment failure is multidrug resistance (MDR) phenomenon. The current study aims to explain the mechanisms involved in multidrug resistance of childhood ALL, and introduces ATP-binding cassette transporterA2 (ABCA2) as an ABC transporter gene which may have a high impact on MDR. Benefiting fr...

  4. Decreased PARP and procaspase-2 protein levels are associated with cellular drug resistance in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Holleman, Amy; den Boer, Monique L; Kazemier, Karin M; Beverloo, H Berna; von Bergh, Anne R M; Janka-Schaub, Gritta E; Pieters, Rob

    2005-09-01

    Drug resistance in childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) is associated with impaired ability to induce apoptosis. To elucidate causes of apoptotic defects, we studied the protein expression of Apaf-1, procaspases-2, -3, -6, -7, -8, -10, and poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) in cells from children with acute lymphoblastic leukemia (ALL; n = 43) and acute myeloid leukemia (AML; n = 10). PARP expression was present in all B-lineage samples, but absent in 4 of 15 T-lineage ALL samples and 3 of 10 AML cases, which was not caused by genomic deletions. PARP expression was a median 7-fold lower in T-lineage ALL (P < .001) and 10-fold lower in AML (P < .001) compared with B-lineage ALL. PARP expression was 4-fold lower in prednisolone, vincristine and L-asparaginase (PVA)-resistant compared with PVA-sensitive ALL patients (P < .001). Procaspase-2 expression was 3-fold lower in T-lineage ALL (P = .022) and AML (P = .014) compared with B-lineage ALL. In addition, procaspase-2 expression was 2-fold lower in PVA-resistant compared to PVA-sensitive ALL patients (P = .042). No relation between apoptotic protease-activating factor 1 (Apaf-1), procaspases-3, -6, -7, -8, -10, and drug resistance was found. In conclusion, low baseline expression of PARP and procaspase-2 is related to cellular drug resistance in childhood acute lymphoblastic leukemia.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Robert J Weeks

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

  7. Detection of clonality by polymerase chain reaction in childhood B-lineage acute lymphoblastic leukemia.

    Science.gov (United States)

    Januszkiewicz, D A; Nowak, J S

    1994-09-01

    DNA-based PCR with various sets of primers for TCR gamma/delta, and Ig heavy chain (IgH) genes were used to study clonality in childhood B-lineage acute lymphoblastic leukemia. Amplification of the IgH CDR-III was observed in 75 of 120 analyzed cases (62.5%). From all analyzed groups, the IgH gene rearrangement was most often observed in pre-B ALL (85.7%) and was rather rare in null-ALL (34.5%). TCR delta gene rearrangement was the most common, and was observed in 77 patients (64.2%). The typical pattern of rearrangements was defined as an incomplete V delta 2 to D delta 3, V delta 2 to D delta 2, or D delta 3 to D delta 2 recombination product. Rearrangements of TCR gamma gene we observed in 61 cases (50.8%). TCR gamma gene rearrangements were detected predominantly in null-ALL and early B-ALL (55.2% and 60%, respectively) and were rather rare in other groups. Of all eight V segments of V gamma I group, the most frequent gene usage concerns regions V gamma 2, V gamma 4, and psi V gamma 7. We have confirmed that IgH gene amplification, together with TCR gamma and delta gene amplification, provides a rapid, sensitive approach to assessing clonality in ALL almost in 100% of cases.

  8. Prospective Evaluation of Whole Genome MicroRNA Expression Profiling in Childhood Acute Lymphoblastic Leukemia

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    Muhterem Duyu

    2014-01-01

    Full Text Available Dysregulation of microRNA (miRNA expression contributes to the pathogenesis of several clinical conditions. The aim of this study is to evaluate the associations between miRNAs and childhood acute lymphoblastic leukemia (ALL to discover their role in the course of the disease. Forty-three children with ALL and 14 age-matched healthy controls were included in the study. MicroRNA microarray expression profiling was used for peripheral blood and bone marrow samples. Aberrant miRNA expressions associated with the diagnosis and outcome were prospectively evaluated. Confirmation analysis was performed by real time RT-PCR. miR-128, miR-146a, miR-155, miR-181a, and miR-195 were significantly dysregulated in ALL patients at day 0. Following a six-month treatment period, the change in miRNA levels was determined by real time RT-PCR and expression of miR-146a, miR-155, miR-181a, and miR-195 significantly decreased. To conclude, these miRNAs not only may be used as biomarkers in diagnosis of ALL and monitoring the disease but also provide new insights into the potential roles of them in leukemogenesis.

  9. Childhood T-cell acute lymphoblastic leukaemia expressing "Ia-like" antigen:" a case report.

    Science.gov (United States)

    Kupa, A; Beckman, I G; Bradley, J; Moore, H; Thomas, M; Zola, H; Cheney, K; Rice, M; Toogood, I

    1982-01-01

    A 4-year-old girl presenting with vomiting, abdominal pain, and renal failure was found to have gross hepatosplenomegaly, a renal mass, and bilateral pleural effusions. A diagnosis of acute lymphoblastic leukaemia (ALL) was suggested by a peripheral white cell count (WCC) of 119,000 x 10(6)mm3, 57% blasts, 22% lymphocytes, and confirmed by bone marrow examination. Lymphocyte surface marker studies at diagnosis enabled classification as a T-ALL, with a significant proportion of the T cells also bearing receptors for the third component of complement (C3). Seventy-two percent of the peripheral blood mononuclear cells reacted with anti-Ia monoclonal antibody (FMC44), and a smaller proportion (25%) carried receptors for the Fc portion of IgG. The T-classification of this ALL was verified at central nervous system (CNS) relapse and at a subsequent nodal relapse. Double-marker studies on cells from the infiltrated lymph node prepared in suspension confirmed the presence of Ia-positive T cells. The Ia marker is usually a useful discriminant between T and non-T cells in normal and ALL cell populations. The case described here highlights the need for a panel of markers to be used in classification of childhood ALL and supports the suggestion that there is a distinct subtype of Ia-positive T-ALL.

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

    Science.gov (United States)

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

    2013-01-01

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

  11. Improved flow cytometric detection of minimal residual disease in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Denys, B.; van der Sluijs-Gelling, A. J.; Homburg, C.; van der Schoot, C. E.; de Haas, V.; Philippe, J.; Pieters, R.; van Dongen, J. J. M.; van der Velden, V. H. J.

    2013-01-01

    Most current treatment protocols for acute lymphoblastic leukemia (ALL) include minimal residual disease (MRD) diagnostics, generally based on PCR analysis of rearranged antigen receptor genes. Although flow cytometry (FCM) can be used for MRD detection as well, discordant FCM and PCR results are ob

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  13. Chemotherapy-Related Side Effects in Childhood Acute Lymphoblastic Leukemia in Indonesia: Parental Perceptions

    NARCIS (Netherlands)

    Sitaresmi, M.N.; Mostert, S.; Purwanto, I.; Gundy, C.; Sutaryo, N.N.; Veerman, A.J.P.

    2009-01-01

    Noncompliance with prescribed medication has been associated with increased chance of relapse and poor outcome. Side effects may be an important cause of noncompliance. Fifty-one parents of children with acute lymphoblastic leukemia in a tertiary care hospital in Indonesia were interviewed about the

  14. Hypothalamic-pituitary-adrenal axis function in survivors of childhood acute lymphoblastic leukemia and healthy controls.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Bierings, M.B.; Hoogerbrugge, P.M.; Ven, P.M. van de; Heijnen, C.J.; Kaspers, G.J.L.

    2012-01-01

    Of all malignancies in children, acute lymphoblastic leukemia (ALL) is the most common type. Since survival significantly improves over time, treatment-related side effects become increasingly important. Glucocorticoids play an important role in the treatment of ALL, but they may suppress the hypoth

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

    NARCIS (Netherlands)

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

    2004-01-01

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

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  17. Reduced folate carrier mutations are not the mechanism underlying methotrexate resistance in childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Kaufman, Y; Drori, S.; Cole, PD; Kamen, BA; Sirota, J; Ifergan, I; Arush, MW; Elhasid, R; Sahar, D; Kaspers, G.J.L.; Jansen, G.; Matherly, LH; Rechavi, G; Toren, A; Assaraf, Y.G.

    2004-01-01

    BACKGROUND: Although the majority of children with acute lymphoblastic leukemia (ALL) are cured with combination chemotherapy containing methotrexate (MTX), drug resistance contributes to treatment failure for a substantial fraction of patients. The primary transporter for folates and MTX is the red

  18. Endocrine Effects of the Treatment for Acute Lymphoblastic Leukemia and Hodgkin’s Lymphoma in Childhood

    NARCIS (Netherlands)

    R.D. van Beek (Robert Diederik)

    2010-01-01

    textabstractOne quarter of all cases of pediatric malignancies is acute Lymphoblastic leukemia (ALL). Per year approximately 4 in 100.000 children are diagnosed with ALL. The disease has a peak incidence between the third and sixth year of life. Predisposing factors for ALL are Down syndrome, Fancon

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2011-08-01

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

  1. Endocrinological and Cardiological Late Effects Among Survivors of Childhood Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Hale Ören

    2013-09-01

    Full Text Available Objective: Survival rates for childhood acute lymphoblastic leukemia (ALL have significantly improved and late effects of therapy have been important in the follow-up of survivors. The objective of this study is to identify the endocrinological and cardiological late effects of ALL patients treated in our pediatric hematology unit. Materials and Methods: Patients treated for ALL with BFM protocols after at least 5 years of diagnosis and not relapsed were included in the study. Endocrinological late effects (growth failure, obesity, insulin resistance, dyslipidemia, thyroid gland disorders, osteopenia/osteoporosis, and pubertal disorders and cardiological late effects were evaluated. The study group was evaluated with anthropometric measurements, body mass index, and laboratory testing of fasting glucose, insulin, serum lipids, thyroid functions, and bone mineral densities. Echocardiography and pulsed wave Doppler imaging were performed for analysis of cardiac functions. Results: Of the 38 ALL survivors, at least 1 adverse event occurred in 23 (60%, with 8 of them (21% having multiple problems. Six (16% of the survivors were obese and 8 (21% of them were overweight. Subjects who were overweight or obese at the time of diagnosis were more likely to be overweight or obese at last follow-up. Obesity was more frequently determined in patients who were younger than 6 years of age at the time of diagnosis. Insulin resistance was observed in 8 (21% subjects. Insulin resistance was more frequently seen in subjects who had family history of type 2 diabetes mellitus. Hyperlipidemia was detected in 8 (21% patients. Hypothyroidism or premature thelarche were detected in 2 children. Two survivors had osteopenia. Cardiovascular abnormalities occurred in one of the subjects with hypertension and cardiac diastolic dysfunction. Conclusion: We point out the necessity of follow-up of these patients for endocrinological and cardiological late effects, since at least

  2. Evaluation of functional RAGE gene polymorphisms in childhood acute lymphoblastic leukemia-A case-control study from Iran.

    Science.gov (United States)

    Eskandari-Nasab, Ebrahim; Hashemi, Mohammad; Hasani, Seyed-Shahab-Adin; Naderi, Majid; Sadeghi-Bojd, Simin; Taheri, Mohsen

    2017-03-04

    We examined the possible relationship between three RAGE polymorphisms, -429C/T, -374 T/A, and 63-bp deletion, and susceptibility to childhood acute lymphoblastic leukemia (ALL) in an Iranian population. This study included 75 ALL patients and 115 healthy subjects. Genotyping was performed using HEXA-ARMS-polymerase chain reaction. We found no significant association among RAGE gene polymorphisms and the risk for ALL at genotype, allelic and haplotype levels (P > 0.05). The hemoglobin levels were higher in patients with RAGE -374 TT than in the TA carriers (P = 0.019). Our results demonstrated that the RAGE gene variations were not associated with risk of pediatrics ALL.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Methotrexate (MTX) eradicates leukemic cells by disrupting de novo nucleotide biosynthesis and DNA replication, resulting in cell death. Since its introduction in 1947, MTX-containing chemotherapeutic regimens have proven instrumental in achieving curative effects in acute lymphoblastic...... leukemia (ALL). However, drug resistance phenomena pose major obstacles to efficacious ALL chemotherapy. Moreover, clinically relevant molecular mechanisms underlying chemoresistance remain largely obscure. Several alterations in MTX metabolism, leading to impaired accumulation of this cytotoxic agent...

  4. The metabolic syndrome in survivors of childhood acute lymphoblastic leukemia in Isfahan, Iran

    Directory of Open Access Journals (Sweden)

    Nahid Reisi

    2009-04-01

    Full Text Available

    • BACKGROUND: To determine the prevalence of metabolic syndrome in survivors of childhood leukemia in Isfahan, Iran.
    • METHODS: During a 4-year period (2003 to 2007, 55 children (33 male and 22 female diagnosed with ALL at Unit of Hematology/ Oncology, Department of Pediatrics, Isfahan University of Medical Science, were enrolled in this crosssectional study. Metabolic syndrome was defined using the modified version of Adult Treatment Panel (ATP III criteria. Insulin resistance was defined based on the homeostasis model assessment index (HOMA-IR.
    • RESULTS: The mean age of participates was 10.4 years (range 6-19 years and the mean interval since completion of chemotherapy was 35 months. Twenty percent (11/55 of survivors (10 male, 1 female met criteria for diagnosis of metabolic syndrome. Obesity was observed in one forth of patients and nearly 3/4 of obese patients had metabolic syndrome. High serum insulin levels were found in 16% of participants and in 63% of obese survivors. The mean insulin levels in survivors with metabolic syndrome was three-times more than those without (28.3 mu/l vs. 9.57 mu/l, p = 0.004. Insulin resistance was detected in 72.7% of survivors with metabolic syndrome and it was  ositively correlated with serum triglycerides (0.543, p < 0.001, systolic and diastolic BP (0.348, p = 0.01 and 0.368, p = 006 respectively, insulin levels (0.914, p < 0.001 and blood sugar (0.398, p = 003.
    • CONCLUSIONS: The prevalence of metabolic syndrome in survivors of childhood leukemia in Iran is higher than developed countries. Nearly all of the obese patients had metabolic syndrome. Weight control and regular physical exercise are recommended to the survivors.
    • KEYWORDS: Acute lymphoblastic leukemia, metabolic syndrome, obesity, children.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Children with acute lymphoblastic leukemia (ALL) react very differently to chemotherapy. One explanation for this is inherited genetic variation. The glutathione S-transferase (GST) enzymes inactivate a number of chemotherapeutic drugs administered in childhood ALL therapy. Two multiplexing methods...... were applied for genotyping the GSTM1 and GSTT1 genes (distinguishing between 0, 1, or 2 gene copies) and the GSTP1 313 A>G polymorphism, simultaneously. A total of 263 childhood ALL patients were genotyped. No gene dose effect on outcome was demonstrated with either GST polymorphisms. Grouping of GSTM......1 and GSTT1 into poor (0 or 1 gene copy)-and good metabolizers (at least 2 gene copies)-showed that the poor metabolizers had a trend toward a better outcome (event-free survival = 91.8%) compared with the good metabolizers (event-free survival = 83.2%). Similarly, in the adjusted analysis the good...

  6. The expression of histone deacetylase 4 is associated with prednisone poor-response in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Gruhn, Bernd; Naumann, Thomas; Gruner, Dorothee; Walther, Mario; Wittig, Susan; Becker, Sabine; Beck, James F; Sonnemann, Jürgen

    2013-10-01

    This study aimed at the identification of histone deacetylase (HDAC) isoforms relevant for childhood acute lymphoblastic leukemia (ALL). Expression of HDAC1-11 was determined in 93 primary ALL and eight healthy donor samples. HDAC1, HDAC2 and HDAC8 showed significantly higher expressions in ALL samples. Correlation analysis of HDAC expression with clinicopathological parameters revealed that high HDAC1, HDAC2, HDAC4 and HDAC11 levels were significantly associated with unfavorable prognostic factors. Particularly, high HDAC4 expression was associated with high initial leukocyte count, T cell ALL and prednisone poor-response. siRNA-mediated inhibition of HDAC4 sensitized a T-ALL cell line to etoposide-induced cell death. In conclusion, our data point to HDAC4 as drug target in childhood ALL, especially in prednisone poor-responders.

  7. Minimal Residual Disease Evaluation in Childhood Acute Lymphoblastic Leukemia: An Economic Analysis

    Science.gov (United States)

    Gajic-Veljanoski, O.; Pham, B.; Pechlivanoglou, P.; Krahn, M.; Higgins, Caroline; Bielecki, Joanna

    2016-01-01

    Background Minimal residual disease (MRD) testing by higher performance techniques such as flow cytometry and polymerase chain reaction (PCR) can be used to detect the proportion of remaining leukemic cells in bone marrow or peripheral blood during and after the first phases of chemotherapy in children with acute lymphoblastic leukemia (ALL). The results of MRD testing are used to reclassify these patients and guide changes in treatment according to their future risk of relapse. We conducted a systematic review of the economic literature, cost-effectiveness analysis, and budget-impact analysis to ascertain the cost-effectiveness and economic impact of MRD testing by flow cytometry for management of childhood precursor B-cell ALL in Ontario. Methods A systematic literature search (1998–2014) identified studies that examined the incremental cost-effectiveness of MRD testing by either flow cytometry or PCR. We developed a lifetime state-transition (Markov) microsimulation model to quantify the cost-effectiveness of MRD testing followed by risk-directed therapy to no MRD testing and to estimate its marginal effect on health outcomes and on costs. Model input parameters were based on the literature, expert opinion, and data from the Pediatric Oncology Group of Ontario Networked Information System. Using predictions from our Markov model, we estimated the 1-year cost burden of MRD testing versus no testing and forecasted its economic impact over 3 and 5 years. Results In a base-case cost-effectiveness analysis, compared with no testing, MRD testing by flow cytometry at the end of induction and consolidation was associated with an increased discounted survival of 0.0958 quality-adjusted life-years (QALYs) and increased discounted costs of $4,180, yielding an incremental cost-effectiveness ratio (ICER) of $43,613/QALY gained. After accounting for parameter uncertainty, incremental cost-effectiveness of MRD testing was associated with an ICER of $50,249/QALY gained. In

  8. Treatment of childhood T-cell lymphoblastic lymphoma according to the strategy for acute lymphoblastic leukaemia, without radiotherapy: long term results of the EORTC CLG 58881 trial.

    Science.gov (United States)

    Uyttebroeck, Anne; Suciu, Stefan; Laureys, Geneviève; Robert, Alain; Pacquement, Hélène; Ferster, Alina; Marguerite, Geneviève; Mazingue, Françoise; Renard, Marleen; Lutz, Patrick; Rialland, Xavier; Mechinaud, Françoise; Cavé, Hélène; Baila, Liliana; Bertrand, Yves

    2008-04-01

    From June 1989 through to November 1998, 121 children with newly diagnosed T-cell lymphoblastic lymphoma (T-LBL) were included in the EORTC 58881 trial conducted by the Children's Leukaemia Group. The therapy regimen was based on a Berlin-Frankfurt-Munster protocol, for a total duration of 24 months. Cranial irradiation, prophylactic cranial and local, was omitted, even for patients with central nervous involvement at diagnosis. In total, 119 patients were evaluable. The median follow-up was 6.7 years. The overall event-free survival (EFS) rate at 6 years was 77.5% (standard error (SE)=4%). Median time of relapse was 1 year after complete remission (range 0.2-5.9 years). Only two (1.8%) patients had an isolated central nervous system relapse. For patients with complete response (n=16) to the 7-day prephase, the EFS rate at 6 years was 100% versus 14% (P<0.001) for patients with no response (n=7). Overall survival rate at 6 years was 86% (SE=3%). An intensive acute lymphoblastic leukaemia type chemotherapy regimen without irradiation leads to a high cure and survival rate in childhood T-LBL without an increased CNS recurrence. This suggests that prophylactic cranial irradiation can safely be omitted. Response to the prephase appeared to be a strong prognostic factor for EFS.

  9. Late recurrence of childhood T-cell acute lymphoblastic leukemia frequently represents a second leukemia rather than a relapse: first evidence for genetic predisposition

    NARCIS (Netherlands)

    Szczepanski, T.; Velden, V.H. van der; Waanders, E.; Kuiper, R.P.; Vlierberghe, P. Van; Gruhn, B.; Eckert, C.; Panzer-Grumayer, R.; Basso, G.; Cave, H.; Stadt, U.Z.; Campana, D.; Schrauder, A.; Sutton, R.; Wering, E. van; Meijerink, J.P.P.; Dongen, J.J. van

    2011-01-01

    PURPOSE: Relapse of childhood T-cell acute lymphoblastic leukemia (T-ALL) often occurs during treatment, but in some cases, leukemia re-emerges off therapy. On the basis of previous analyses of T-cell receptor (TCR) gene rearrangement patterns, we hypothesized that some late recurrences of T-ALL mig

  10. The Circadian Schedule for Childhood Acute Lymphoblastic Leukemia Maintenance Therapy does not Influence Event-Free Survival in the NOPHO ALL92 Protocol

    DEFF Research Database (Denmark)

    Clemmensen, Kim K. B.; Christensen, Regitse H.; Shabaneh, Diana N.;

    2014-01-01

    BACKGROUND: The event-free survival of childhood acute lymphoblastic leukemia (ALL) has been reported to be superior when oral methotrexate (MTX) and 6-mercaptopurine (6MP) maintenance therapy (MT) is administered in the evening compared to the morning. PROCEDURE: In the ALL92 MT study we prospec...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Prognostic impact of peripheral blood white blood cell count (WBC) at the diagnosis of childhood acute lymphoblastic leukaemia (ALL) was evaluated in a population-based consecutive series of 2666 children aged 1–15 treated for ALL between 1992 and 2008 in the five Nordic countries (Denmark, Finland...

  12. Poor adherence to dietary guidelines among adult survivors of childhood acute lymphoblastic leukemia

    OpenAIRE

    Robien, Kim; Ness, Kirsten K.; Klesges, Lisa M.; Baker, K. Scott; Gurney, James G.

    2008-01-01

    Recent studies indicate that survivors of childhood acute lymphocytic leukemia (ALL) are at increased risk of obesity and cardiovascular disease, conditions that healthy dietary patterns may help ameliorate or prevent. To evaluate the usual dietary intake of adult survivors of childhood ALL, food frequency questionnaire data were collected from 72 participants, and compared with the 2007 WCRF/AICR Cancer Prevention recommendations, the DASH diet, and the 2005 USDA Food Guide. Mean daily energ...

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

    Directory of Open Access Journals (Sweden)

    Skegg David CG

    2007-07-01

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

  14. Disruption of Learning Processes by Chemotherapeutic Agents in Childhood Survivors of Acute Lymphoblastic Leukemia and Preclinical Models

    Directory of Open Access Journals (Sweden)

    Emily B. Bisen-Hersh, Philip N. Hineline, Ellen A. Walker

    2011-01-01

    Full Text Available Objective: With the survival rate of acute lymphoblastic leukemia (ALL surpassing 90 percent within this decade, new research is emerging in the field of late effects. A review of the research investigating the relationship of treatment regimens for ALL to specific late effect deficits, underlying mechanisms, and possible remediation is warranted to support continued studies.Methods: The clinical literature was briefly surveyed to describe the occurrence and topography of late effects, specifically neurocognitive deficits. Additionally, the preclinical literature was reviewed to uncover potential underlying mechanisms of these deficits. The advantages of using rodent models to answer these questions are outlined, as is an assessment of the limited number of rodent models of childhood cancer treatment.Results: The literature supports that childhood survivors of ALL exhibit academic difficulties and are more likely to be placed in a special education program. Behavioral evidence has highlighted impairments in the areas of attention, working memory, and processing speed, leading to a decrease in full scale IQ. Neurophysiological and preclinical evidence for these deficits has implicated white matter abnormalities and acquired brain damage resulting from specific chemotherapeutic agents commonly used during treatment.Conclusions: The exact role of chemotherapeutic agents in learning deficits remains mostly unknown. Recommendations for an improved rodent model of learning deficits in childhood cancer survivors are proposed, along with suggestions for future directions in this area of research, in hopes that forthcoming treatment regimens will reduce or eliminate these types of impairments.

  15. Maternal benzene exposure during pregnancy and risk of childhood acute lymphoblastic leukemia: a meta-analysis of epidemiologic studies.

    Directory of Open Access Journals (Sweden)

    Yanfeng Zhou

    Full Text Available The prevalence of childhood leukemia is increasing rapidly all over the world. However, studies on maternal benzene exposure during pregnancy and childhood acute lymphoblastic leukemia (ALL have not been systematically assessed. Therefore, we performed a meta-analysis to investigate the association between maternal solvent, paint, petroleum exposure, and smoking during pregnancy and risk of childhood ALL.Relevant studies up to September 1st, 2013 were identified by searching the PubMed, EMBASE, Cochrane library and the Web of Science databases. The effects were pooled using either fixed or random effect models based on the heterogeneity of the studies.Twenty-eight case-control studies and one cohort study were included for analysis, with a total of 16,695 cases and 1,472,786 controls involved. Pooled odds ratio (OR with 95% confidence interval (CI for ALL was 1.25 (1.09, 1.45 for solvent, 1.23 (1.02, 1.47 for paint, 1.42 (1.10, 1.84 for petroleum exposure, and 0.99 (0.93, 1.06 for maternal smoking during pregnancy. No publication bias was found in this meta-analysis and consistent results were observed for subgroup and sensitivity analyses.Childhood ALL was associated with maternal solvent, paint, and petroleum exposure during pregnancy. No association was found between ALL and maternal smoking during pregnancy. Avoidance of maternal occupational and environmental benzene exposure during pregnancy could contribute to a decrease in the risk of childhood ALL.

  16. Post chemotherapy blood and bone marrow regenerative changes in childhood acute lymphoblastic leukemia a prospective study

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    Rashmi Kushwaha

    2014-01-01

    Full Text Available Context: This study was done to assess the Serial peripheral blood and bone marrow changes in patients of Acute Lymphoblastic Leukemia on chemotherapy. Aims: To assess the therapy related serial bone marrow changes in patients of Acute Lymphoblastic Leukemia. Settings and Design: Prospective study, carried out in Lymphoma- Leukemia Lab, Department of Pathology, K.G.M.U from March 2011 to March 2012. A total of 60 cases were studied Materials and Methods: History, complete hemogram, bone marrow examination at pretherapy (Day-0, intratherapy (Day-14, and end of induction chemotherapy (Day-28 were done. Peripheral blood smears were evaluated at regular interval to assess clearance of blast cells. Statistical analysis used: The statistical analysis was done using SPSS (Statistical Package for Social Sciences Version 15.0 statistical Analysis Software. The values were represented in Number (% and Mean ± SD. The following Statistical formulas were used: Mean, standard deviation, Chi square test, Paired "t" test, Student ′t′ test, Level of significance P Results: Incidence of ALL-L1 (46.7% and ALL-L2 (53.3% was equal. ALL-L2 patients had poor survival.Day 0 (D-0 bone marrow was hypercellular with flooding of marrow by leukemic cells. High levels of tumor load at D′0′ were associated with poor survival. 14 th day of Induction phase showed significant decrease in hemoglobin and TLC as compared to D ′0′ parameters. D28 showed marrow regeneration. Cellularity, Blast%, and Leukemic Index showed significant drop from day ′0′ to day 14 due to myelosupression, whereas regeneration reflected by increased cellularity as per day 28 marrow. Lymphocytosis (>20% at end of induction chemotherapy had better survival and longer remission.Risk of mortality was directly proportional to blast clearance and was a major independent prognostic factor for achievement of complete remission. Conclusions: A bone marrow examination at the end of induction

  17. Family characteristics as risk factors for childhood acute lymphoblastic leukemia: a population-based case-control study.

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    Martin Feller

    Full Text Available BACKGROUND: To date, few risk factors for childhood acute lymphoblastic leukemia (ALL have been confirmed and the scientific literature is full of controversial "evidence." We examined if family characteristics, particularly maternal and paternal age and number of older siblings, were risk factors for childhood acute lymphoblastic leukemia (ALL. METHODOLOGY/PRINCIPAL FINDINGS: In this population-based nationwide matched case-control study, patients 0-14 years of age with ALL diagnosed 1991-2006 and registered in the Swiss Childhood Cancer Registry were linked with their census records of 1990 and 2000. Eight controls per case were selected from the census. The association between family characteristics and ALL was analyzed by conditional logistic regressions. We found that increasing maternal age was associated with incidence of ALL in the offspring (OR per 5-year increase in maternal age 1.18, 95% CI 1.05-1.31; p = 0.004, remaining stable (trend OR 1.14, 95% CI 0.99-1.31; p = 0.060 after adjustment for other risk factors. The association with paternal age was weaker (OR per 5-year increase 1.14, 95% CI 1.01-1.28, p = 0.032 and disappeared after adjustments. Number of older siblings was not associated with risk of ALL in the overall group of children aged 0-14 years at diagnosis. However, we found a negative trend between number of older siblings and ALL diagnosed at age 0-4 years (OR per sibling 0.85, 95% CI 0.68-1.06; p = 0.141 and a positive trend for ALL diagnosed at age 5-9 (OR 1.34, 95% CI 1.05-1.72; p = 0.019, with some evidence for an effect modification (p-value for interaction  = 0.040. CONCLUSIONS: As in other studies, increasing maternal, but not paternal age was associated with risk of ALL. We found only a weak association with the number of older siblings, suggesting a delay in disease manifestation rather than a decrease in incidence.

  18. Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2016-12-28

    B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; BCR-ABL1 Fusion Protein Expression; Minimal Residual Disease; Philadelphia Chromosome Positive; T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  19. Testicular relapse in childhood acute lymphoblastic leukemia: The challenges and lessons

    Directory of Open Access Journals (Sweden)

    K P Kulkarni

    2010-01-01

    Full Text Available Background : Relapse of disease is documented in 15-20% of children with acute lymphoblastic leukemia (ALL. Although testicular relapse is rare with modern risk-adapted treatment protocols, earlier, the testes were a frequently encountered site of relapse and were designated as "drug sanctuaries". Purpose : This descriptive study was designed to assess the pattern of testicular relapse and to identify high-risk factors. Materials and Methods : Data obtained from case records of 407 boys with ALL were analyzed. Fine needle aspiration cytology was carried out in children presenting with painless enlargement of testi(es. Bone marrow aspiration and cerebrospinal fluid examination were performed concomitantly to confirm or exclude disease at these sites. Results : Testicular relapse was documented in 30 boys. It was isolated in 17 patients and associated with bone marrow and/or central nervous system relapse in 13. At relapse, nine boys were over the age of 10 years. The majority were very early and early relapsers. Hyperleucocytosis was documented in five of 30 and seven of 137 relapsers and nonrelapsers, respectively (P = 0.04. Twelve of the 30 boys with testicular relapse were treated with testicular irradiation, reinduction and maintenance therapy. The estimated median overall survival was 33 months. Conclusion : Testicular relapse, which depends on the therapy administered, may manifest several months/years after completion of treatment. The high incidence of testicular relapse in our series implicates the need of revaluation of our protocol and incorporation of high/intermediate dose methotrexate therapy upfront.

  20. Psychological Impact of Chemotherapy for Childhood Acute Lymphoblastic Leukemia on Patients and Their Parents.

    Science.gov (United States)

    Sherief, Laila M; Kamal, Naglaa M; Abdalrahman, Hadel M; Youssef, Doaa M; Abd Alhady, Mohamed A; Ali, Adel S A; Abd Elbasset, Maha Aly; Hashim, Hiatham M

    2015-12-01

    To assess the self-esteem of pediatric patients on chemotherapy for acute lymphoblastic leukemia (ALL) and psychological status of their parents.The psychological status of 178 children receiving chemotherapy for ALL and their parents was assessed using parenting stress index (PSI) to determine the degree of stress the parents are exposed to using parent's and child's domains. Self-esteem Scale was used to determine the psychological status of patients.The study revealed significant low level of self-esteem in 84.83% of patients. Their parents had significant psychological stress. PSI was significantly associated with parents' low sense of competence, negative attachment to their children, feeling of high restriction, high depression, poor relation to spouse, high social isolation variables of parent's domains. It was significantly associated with low distraction, negative parents' reinforcement, low acceptability, and high demanding variables of child's domains. Long duration of disease was the most detrimental factor among demographic data of the patients.Chemotherapy for ALL has a significant impact on the psychological status of both patients and their parents with high prevalence of low self-esteem in children and high degree of stress in their parents.

  1. Confirmation of childhood acute lymphoblastic leukemia variants, ARID5B and IKZF1, and interaction with parental environmental exposures.

    Directory of Open Access Journals (Sweden)

    Tiffany-Jane Evans

    Full Text Available Genome wide association studies (GWAS have established association of ARID5B and IKZF1 variants with childhood acute lymphoblastic leukemia (ALL. Epidemiological studies suggest that environmental factors alone appear to make a relatively minor contribution to disease risk. The polygenic nature of childhood ALL predisposition together with the timing of environmental triggers may hold vital clues for disease etiology. This study presents results from an Australian GWAS of childhood ALL cases (n = 358 and population controls (n = 1192. Furthermore, we utilised family trio (n = 204 genotypes to extend our investigation to gene-environment interaction of significant loci with parental exposures before conception, and child's sex and age. Thirteen SNPs achieved genome wide significance in the population based case/control analysis; ten annotated to ARID5B and three to IKZF1. The most significant SNPs in these regions were ARID5B rs4245595 (OR 1.63, CI 1.38-1.93, P = 2.13×10(-9, and IKZF1 rs1110701 (OR 1.69, CI 1.42-2.02, p = 7.26×10(-9. There was evidence of gene-environment interaction for risk genotype at IKZF1, whereby an apparently stronger genetic effect was observed if the mother took folic acid or if the father did not smoke prior to pregnancy (respective interaction P-values: 0.04, 0.05. There were no interactions of risk genotypes with age or sex (P-values >0.2. Our results evidence that interaction of genetic variants and environmental exposures may further alter risk of childhood ALL however, investigation in a larger population is required. If interaction of folic acid supplementation and IKZF1 variants holds, it may be useful to quantify folate levels prior to initiating use of folic acid supplements.

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

    Science.gov (United States)

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

    2016-10-01

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

  3. Neurocognitive Outcomes in Long-term Survivors of Childhood Acute Lymphoblastic Leukemia Treated on Contemporary Treatment Protocols: A Systematic Review

    Science.gov (United States)

    Cheung, Yin Ting; Krull, Kevin R.

    2015-01-01

    The intensified administration of chemotherapeutic drugs has gradually replaced cranial radiation therapy (CRT) for the treatment of childhood acute lymphoblastic leukemia (ALL). While CRT is often implicated in neurocognitive impairment in ALL survivors, there is a paucity of literature that evaluates the persistence of neurocognitive deficits in long-term survivors of pediatric ALL who were treated with contemporary chemotherapy-only protocols. Results from this systematic review concurred to the probable cognitive-sparing effect of chemotherapy-based protocols over CRT in long-term survivors. However, coupled with multiple intrinsic and extrinsic factors, survivors who received chemotherapy treatment still suffered from apparent cognitive impairment, particularly in the attention and executive function domains. Notably, there is evidence to suggest that the late neurotoxic effect of methotrexate on survivors’ neurocognitive performance may be dose-related. This review also recommends future pharmacokinetic, neuroimaging and genetic studies to illuminate the multifactorial nature of this subject matter and discusses the potential value of neurochemical, physiological, inflammatory and genetic markers for the prediction of susceptibility to neurocognitive impairment in long-term survivors of childhood ALL. PMID:25857254

  4. Breastfeeding and nutrition to 2 years of age and risk of childhood acute lymphoblastic leukemia and brain tumors.

    Science.gov (United States)

    Greenop, Kathryn R; Bailey, Helen D; Miller, Margaret; Scott, Rodney J; Attia, John; Ashton, Lesley J; Downie, Peter; Armstrong, Bruce K; Milne, Elizabeth

    2015-01-01

    Acute lymphoblastic leukemia (ALL) and childhood brain tumors (CBT) are 2 of the most common forms of childhood cancer, but little is known of their etiology. In 2 nationwide case-control studies we investigated whether breastfeeding, age of food introduction, or early diet are associated with the risk of these cancers. Cases aged 0-14 years were identified from Australian pediatric oncology units between 2003 and 2007 (ALL) and 2005 and 2010 (CBT) and population-based controls through nationwide random-digit dialing. Mothers completed questionnaires giving details of infant feeding up to the age of 2 yr. Data from 322 ALL cases, 679 ALL controls, 299 CBT cases, and 733 CBT controls were analysed using unconditional logistic regression. Breastfeeding was associated with a reduced risk of ALL [odds ratio (OR) = 0.52, 95% confidence interval (CI): 0.32, 0.84), regardless of duration. Introduction of artificial formula within 14 days of birth was positively associated with ALL (OR = 1.57, 95% CI: 1.03, 2.37), as was exclusive formula feeding to 6 mo (OR = 1.81, 95% CI: 1.07, 3.05). No associations were seen between breastfeeding or formula use and risk of CBT. Our results suggest that breastfeeding and delayed introduction of artificial formula may reduce the risk of ALL but not CBT.

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

    Science.gov (United States)

    2013-10-29

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

  6. Neurocognitive Outcomes Decades After Treatment for Childhood Acute Lymphoblastic Leukemia: A Report From the St Jude Lifetime Cohort Study

    Science.gov (United States)

    Krull, Kevin R.; Brinkman, Tara M.; Li, Chenghong; Armstrong, Gregory T.; Ness, Kirsten K.; Srivastava, Deo Kumar; Gurney, James G.; Kimberg, Cara; Krasin, Matthew J.; Pui, Ching-Hon; Robison, Leslie L.; Hudson, Melissa M.

    2013-01-01

    Purpose To determine rates, patterns, and predictors of neurocognitive impairment in adults decades after treatment for childhood acute lymphoblastic leukemia (ALL). Patients and Methods Survivors of childhood ALL treated at St Jude Children's Research Hospital who were still alive at 10 or more years after diagnosis and were age ≥ 18 years were recruited for neurocognitive testing. In all, 1,014 survivors were eligible, 738 (72.8%) agreed to participate, and 567 (76.8%) of these were evaluated. Mean age was 33 years; mean time since diagnosis was 26 years. Medical record abstraction was performed for data on doses of cranial radiation therapy (CRT) and cumulative chemotherapy. Multivariable modeling was conducted and glmulti package was used to select the best model with minimum Akaike information criterion. Results Impairment rates across neurocognitive domains ranged from 28.6% to 58.9%, and those treated with chemotherapy only demonstrated increased impairment in all domains (all P values < .006). In survivors who received no CRT, dexamethasone was associated with impaired attention (relative risk [RR], 2.12; 95% CI, 1.11 to 4.03) and executive function (RR, 2.42; 95% CI, 1.20 to 4.91). The impact of CRT was dependent on young age at diagnosis for intelligence, academic, and memory functions. Risk for executive function problems increased with survival time in a CRT dose-dependent fashion. In all survivors, self-reported behavior problems increased by 5% (RR, 1.05; 95% CI, 1.01 to 1.09) with each year from diagnosis. Impairment was associated with reduced educational attainment and unemployment. Conclusion This study demonstrates persistent and significant neurocognitive impairment in adult survivors of childhood ALL and warrants ongoing monitoring of brain health to facilitate successful adult development and to detect early onset of decline as survivors mature. PMID:24190124

  7. Multiple drug resistance protein (MDR-1, multidrug resistance-related protein (MRP and lung resistance protein (LRP gene expression in childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Elvis Terci Valera

    Full Text Available CONTEXT: Despite the advances in the cure rate for acute lymphoblastic leukemia, approximately 25% of affected children suffer relapses. Expression of genes for the multiple drug resistance protein (MDR-1, multidrug resistance-related protein (MRP, and lung resistance protein (LRP may confer the phenotype of resistance to the treatment of neoplasias. OBJECTIVE: To analyze the expression of the MDR-1, MRP and LRP genes in children with a diagnosis of acute lymphoblastic leukemia via the semiquantitative reverse transcription polymerase chain reaction (RT-PCR, and to determine the correlation between expression and event-free survival and clinical and laboratory variables. DESIGN: A retrospective clinical study. SETTING: Laboratory of Pediatric Oncology, Department of Pediatrics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil. METHODS: Bone marrow aspirates from 30 children with a diagnosis of acute lymphoblastic leukemia were assessed for the expression of messenger RNA for the MDR-1, MRP and LRP genes by semi-quantitative RT-PCR. RESULTS: In the three groups studied, only the increased expression of LRP was related to worsened event-free survival (p = 0.005. The presence of the common acute lymphoblastic leukemia antigen (CALLA was correlated with increased LRP expression (p = 0.009 and increased risk of relapse or death (p = 0.05. The relative risk of relapse or death was six times higher among children with high LRP expression upon diagnosis (p = 0.05, as confirmed by multivariate analysis of the three genes studied (p = 0.035. DISCUSSION: Cell resistance to drugs is a determinant of the response to chemotherapy and its detection via RT-PCR may be of clinical importance. CONCLUSIONS: Evaluation of the expression of genes for resistance to antineoplastic drugs in childhood acute lymphoblastic leukemia upon diagnosis, and particularly the expression of the LRP gene, may be of clinical relevance, and should be the

  8. A childhood acute lymphoblastic leukemia genome-wide association study identifies novel sex-specific risk variants

    Science.gov (United States)

    Singh, Sandeep K.; Lupo, Philip J.; Scheurer, Michael E.; Saxena, Anshul; Kennedy, Amy E.; Ibrahimou, Boubakari; Barbieri, Manuel Alejandro; Mills, Ken I.; McCauley, Jacob L.; Okcu, Mehmet Fatih; Dorak, Mehmet Tevfik

    2016-01-01

    Abstract Childhood acute lymphoblastic leukemia (ALL) occurs more frequently in males. Reasons behind sex differences in childhood ALL risk are unknown. In the present genome-wide association study (GWAS), we explored the genetic basis of sex differences by comparing genotype frequencies between male and female cases in a case-only study to assess effect-modification by sex. The case-only design included 236 incident cases of childhood ALL consecutively recruited at the Texas Children's Cancer Center in Houston, Texas from 2007 to 2012. All cases were non-Hispanic whites, aged 1 to 10 years, and diagnosed with confirmed B-cell precursor ALL. Genotyping was performed using the Illumina HumanCoreExome BeadChip on the Illumina Infinium platform. Besides the top 100 statistically most significant results, results were also analyzed by the top 100 highest effect size with a nominal statistical significance (P pregnancy, at birth, childhood, and adolescence. cg22485289 is one of the hypomethylated CpG sites in ALL compared with pre-B cells. Two missense SNPs, rs12722042 and 12722039, in the HLA-DQA1 gene yielded the highest effect sizes (odds ratio [OR] ∼ 14; P <0.01) for sex-specific results. The HLA-DQA1 SNPs belong to DQA1∗01 and confirmed the previously reported male-specific association with DQA1∗01. This finding supports the proposed infection-related etiology in childhood ALL risk for males. Further analyses revealed that most SNPs (either direct effect or through linkage disequilibrium) were within active enhancers or active promoter regions and had regulatory effects on gene expression levels. Cumulative data suggested that RASSF2 rs4813720, which correlates with increased RASSF2 expression, may counteract the suppressor effect of estrogen-regulated miR-17-92 on RASSF2 resulting in protection in males. Given the amount of sex hormone-related mechanisms suggested by our findings, future studies should examine prenatal or early postnatal programming by

  9. Identification of residual leukemic cells by flow cytometry in childhood B-cell precursor acute lymphoblastic leukemia: verification of leukemic state by flow-sorting and molecular/cytogenetic methods

    OpenAIRE

    2012-01-01

    Reduction in minimal residual disease, measured by real-time quantitative PCR or flow cytometry, predicts prognosis in childhood B-cell precursor acute lymphoblastic leukemia. We explored whether cells reported as minimal residual disease by flow cytometry represent the malignant clone harboring clone-specific genomic markers (53 follow-up bone marrow samples from 28 children with B-cell precursor acute lymphoblastic leukemia). Cell populations (presumed leukemic and non-leukemic) were flow-s...

  10. Prognostic value of MRD-dynamics in childhood acute lymphoblastic leukemia treated according to the MB-2002/2008 protocols.

    Science.gov (United States)

    Meleshko, Alexander N; Savva, Natalia N; Fedasenka, Uladzimir U; Romancova, Alexandra S; Krasko, Olga V; Eckert, Cornelia; von Stackelberg, Arend; Aleinikova, Olga V

    2011-10-01

    Detection of minimal residual disease (MRD) during the treatment of acute lymphoblastic leukemia (ALL) by RQ-PCR analysis of clonal Ig/TCR rearrangements is used for risk group stratification in European treatment protocols. In Belarus patients with childhood ALL are treated according to ALL-MB protocols, which do not use MRD-based risk stratification. To evaluate the prognostic significance of MRD for ALL-MB-2002/2008 protocols, MRD was quantified by RQ-PCR in 68 ALL patients at four time points: on day 15, on day 36, before and after maintenance therapy (MT). MRD positivity, as well as quantitative level of MRD were analyzed and compared between patients who stayed in remission and relapsed. Relapse-free survival revealed to be significantly associated with MRD levels at different time points. Unfavorable prognosis was shown for MRD≥10(-3) on day 36 (pPCR in children with ALL treated with ALL-MB protocols is feasible and independently associated with outcome. MRD may be a suitable parameter for treatment stratification in MB protocols in future.

  11. An adult patient who developed malignant fibrous histiocytoma 9 years after radiation therapy for childhood acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Yasuhiro [National Hiroshima Hospital, Higashi-Hiroshima (Japan); Ohno, Norioki; Horikawa, Yoko; Nishimura, Shin-ichiro; Ueda, Kazuhiro; Shimose, Shoji [Hiroshima Univ. (Japan). School of Medicine

    2002-12-01

    A 24-year-old Japanese man with a history of acute lymphoblastic leukemia, which occurred during childhood, developed malignant fibrous histiocytoma of his left knee. His past history revealed that he had undergone leukemic blast cell invasion of the left knee and subsequent radiation therapy 9 years ago. The total radiation doses for the upper part of the left tibia and the lower part of the left femur were 60 Gy and 40 Gy, respectively. Neither distant metastasis nor a relapse of leukemia occurred. A curative resection of the left femur with a noninvasive margin was performed. Adjuvant chemotherapy including high-dose methotrexate was given successfully before and after surgery; this was followed by relapse-free survival for 3 years. The nature of postirradiation malignant fibrous histiocytoma is highly aggressive. When a patient complains of persistent symptoms in a previously irradiated field, the possibility of this tumor must be taken into account. The importance of early diagnosis cannot be over-emphasized. (author)

  12. Chemokines and relapses in childhood acute lymphoblastic leukemia: A role in migration and in resistance to antileukemic drugs.

    Science.gov (United States)

    Gómez, Ana M; Martínez, Carolina; González, Miguel; Luque, Alfonso; Melen, Gustavo J; Martínez, Jesús; Hortelano, Sonsoles; Lassaletta, Álvaro; Madero, Luís; Ramírez, Manuel

    2015-10-01

    We studied whether chemokines may have a role in relapses in childhood acute lymphoblastic leukemia (ALL). We compared the levels of chemokine receptors in marrow samples from 82 children with ALL at diagnosis versus 15 at relapses, and quantified the levels of chemokines in central system fluid (CSF) samples. The functional role of specific chemokines was studied in vitro and in vivo. The expression of some chemokine receptors was upregulated upon leukemic relapse, both in B- and in T-ALL, and in cases of medullary and extramedullary involvement. CXCL10 induced chemotaxis in leukemic cell lines and in primary leukemic cells, depending upon the levels of CXCR3 expression. CXCL10 specifically diminished chemotherapy-induced apoptosis on ALL cells expressing CXCR3, partially inhibiting caspase activation and maintaining the levels of the antiapoptotic protein Bcl-2. Finally, immunodeficient mice engrafted with CXCR3-expressing human leukemic cells showed decreased infiltration of marrow, spleen, and CNS after receiving a CXCR3-antagonist molecule. CXCR3 signaling in ALL may have a dual function: chemotactic for the localisation of leukemic blasts in specific niches, and it may also confer resistance to chemotherapy, enhancing the chances for relapses.

  13. High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

    Science.gov (United States)

    2016-11-14

    Acute Leukemia of Ambiguous Lineage; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  14. Outcome of allogeneic hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia in second complete remission: a single institution study

    Directory of Open Access Journals (Sweden)

    Eun-Jung Lee

    2012-03-01

    Full Text Available Purpose : The survival rate for childhood acute lymphoblastic leukemia (ALL has improved significantly. However, overall prognosis for the 20 to 25% of patients who relapse is poor, and allogeneic hematopoietic stem cell transplantation (HSCT offers the best chance for cure. In this study, we identified significant prognostic variables by analyzing the outcomes of allogeneic HSCT in ALL patients in second complete remission (CR. Methods : Fifty-three ALL patients (42 men, 79% who received HSCT in second CR from August 1991 to February 2009 were included (26 sibling donor HSCTs, 49%; 42 bone marrow transplantations, 79%. Study endpoints included cumulative incidence of acute and chronic graft-versus-host disease (GVHD, relapse, 1-year transplant-related mortality (TRM, disease-free survival (DFS, and overall survival (OS. Results : Cumulative incidences of acute GVHD (grade 2 or above and chronic GVHD were 45.3% and 28.5%, respectively. The estimated 5-year DFS and OS for the cohort was 45.2¡?#?.8%; and 48.3¡?#?%,; respectively. Only donor type, i.e., sibling versus unrelated, showed significant correlation with DFS in multivariate analysis (P=0.010. The rates of relapse and 1 year TRM were 28.9¡?#?.4%; and 26.4¡?#?.1%;, respectively, and unrelated donor HSCT (P=0.002 and HLA mismatch (P =0.022 were significantly correlated with increased TRM in univariate analysis. Conclusion : In this single institution study spanning more than 17 years, sibling donor HSCT was the only factor predicting a favorable result in multivariate analysis, possibly due to increased TRM resulting from unrelated donor HSCT.

  15. Apoptosis induction by Maackia amurensis agglutinin in childhood acute lymphoblastic leukemic cells

    DEFF Research Database (Denmark)

    Kapoor, Sarika; Marwaha, Ram; Majumdar, Siddhartha;

    2007-01-01

    Malignant transformation is known to be associated with changes in cell surface carbohydrate-architecture, which can be detected by lectins. In the present study, Maackia amurensis agglutinin (MAA), specific for NeuNAcalpha(2-->3)Gal/GalNAc showed strong binding with lymphoblasts of children havi...

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

    Aberuyi, N; Rahgozar, S; Moafi, A

    2014-01-01

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

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

    Science.gov (United States)

    Aberuyi, N; Rahgozar, S; Moafi, A

    2014-01-01

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

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

    Science.gov (United States)

    2017-03-27

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

  20. mTOR inhibition by everolimus in childhood acute lymphoblastic leukemia induces caspase-independent cell death.

    Directory of Open Access Journals (Sweden)

    Rana Baraz

    Full Text Available Increasingly, anti-cancer medications are being reported to induce cell death mechanisms other than apoptosis. Activating alternate death mechanisms introduces the potential to kill cells that have defects in their apoptotic machinery, as is commonly observed in cancer cells, including in hematological malignancies. We, and others, have previously reported that the mTOR inhibitor everolimus has pre-clinical efficacy and induces caspase-independent cell death in acute lymphoblastic leukemia cells. Furthermore, everolimus is currently in clinical trial for acute lymphoblastic leukemia. Here we characterize the death mechanism activated by everolimus in acute lymphoblastic leukemia cells. We find that cell death is caspase-independent and lacks the morphology associated with apoptosis. Although mitochondrial depolarization is an early event, permeabilization of the outer mitochondrial membrane only occurs after cell death has occurred. While morphological and biochemical evidence shows that autophagy is clearly present it is not responsible for the observed cell death. There are a number of features consistent with paraptosis including morphology, caspase-independence, and the requirement for new protein synthesis. However in contrast to some reports of paraptosis, the activation of JNK signaling was not required for everolimus-induced cell death. Overall in acute lymphoblastic leukemia cells everolimus induces a cell death that resembles paraptosis.

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

    NARCIS (Netherlands)

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

    2013-01-01

    Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1-18 years with newly diagnosed, t(9; 22)-negative ALL, were

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

    NARCIS (Netherlands)

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

    2013-01-01

    Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1-18 years with newly diagnosed, t(9;22)-negative ALL, were

  3. Assessment of Mercaptopurine (6MP) Metabolites and 6MP Metabolic Key-Enzymes in Childhood Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    Wojtuszkiewicz, A.; Barcelos, A.; Dubbelman, B.; Abreu, R.A. de; Brouwer, C.; Bökkerink, J.P.M.; Haas, V. de; Groot-Kruseman, H. de; Jansen, Gert; Kaspers, G.L.; Cloos, J.; Peters, G.J.

    2014-01-01

    Pediatric acute lymphoblastic leukemia (ALL) is treated with combination chemotherapy including mercaptopurine (6MP) as an important component. Upon its uptake, 6MP undergoes a complex metabolism involving many enzymes and active products. The prognostic value of all the factors engaged in this path

  4. Health-related quality of life in long-term survivors of relapsed childhood acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Stefan Essig

    Full Text Available BACKGROUND: Relapses occur in about 20% of children with acute lymphoblastic leukemia (ALL. Approximately one-third of these children can be cured. Their risk for late effects is high because of intensified treatment, but their health-related quality of life (HRQOL was largely unmeasured. Our aim was to compare HRQOL of ALL survivors with the general population, and of relapsed with non-relapsed ALL survivors. METHODOLOGY/PRINCIPAL FINDINGS: As part of the Swiss Childhood Cancer Survivor Study (SCCSS we sent a questionnaire to all ALL survivors in Switzerland who had been diagnosed between 1976-2003 at age <16 years, survived ≥5 years, and were currently aged ≥16 years. HRQOL was assessed with the Short Form-36 (SF-36, which measures four aspects of physical health and four aspects of mental health. A score of 50 corresponded to the mean of a healthy reference population. We analyzed data from 457 ALL survivors (response: 79%. Sixty-one survivors had suffered a relapse. Compared to the general population, ALL survivors reported similar or higher HRQOL scores on all scales. Survivors with a relapse scored lower in general health perceptions (51.6 compared to those without (55.8;p=0.005, but after adjusting for self-reported late effects, this difference disappeared. CONCLUSION/SIGNIFICANCE: Compared to population norms, ALL survivors reported good HRQOL, even after a relapse. However, relapsed ALL survivors reported poorer general health than non-relapsed. Therefore, we encourage specialists to screen for poor general health in survivors after a relapse and, when appropriate, specifically seek and treat underlying late effects. This will help to improve patients' HRQOL.

  5. Integration of high-resolution methylome and transcriptome analyses to dissect epigenomic changes in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Busche, Stephan; Ge, Bing; Vidal, Ramon; Spinella, Jean-François; Saillour, Virginie; Richer, Chantal; Healy, Jasmine; Chen, Shu-Huang; Droit, Arnaud; Sinnett, Daniel; Pastinen, Tomi

    2013-07-15

    B-cell precursor acute lymphoblastic leukemia (pre-B ALL) is the most common pediatric cancer. Although the genetic determinants underlying disease onset remain unclear, epigenetic modifications including DNA methylation are suggested to contribute significantly to leukemogenesis. Using the Illumina 450K array, we assessed DNA methylation in matched tumor-normal samples of 46 childhood patients with pre-B ALL, extending single CpG-site resolution analysis of the pre-B ALL methylome beyond CpG-islands (CGI). Unsupervised hierarchical clustering of CpG-site neighborhood, gene, or microRNA (miRNA) gene-associated methylation levels separated the tumor cohort according to major pre-B ALL subtypes, and methylation in CGIs, CGI shores, and in regions around the transcription start site was found to significantly correlate with transcript expression. Focusing on samples carrying the t(12;21) ETV6-RUNX1 fusion, we identified 119 subtype-specific high-confidence marker CpG-loci. Pathway analyses linked the CpG-loci-associated genes with hematopoiesis and cancer. Further integration with whole-transcriptome data showed the effects of methylation on expression of 17 potential drivers of leukemogenesis. Independent validation of array methylation and sequencing-derived transcript expression with Sequenom Epityper technology and real-time quantitative reverse transcriptase PCR, respectively, indicates more than 80% empirical accuracy of our genome-wide findings. In summary, genome-wide DNA methylation profiling enabled us to separate pre-B ALL according to major subtypes, to map epigenetic biomarkers specific for the t(12;21) subtype, and through a combined methylome and transcriptome approach to identify downstream effects on candidate drivers of leukemogenesis.

  6. Prognostic significance of bi/oligoclonality in childhood acute lymphoblastic leukemia as determined by polymerase chain reaction

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Scrideli

    2001-09-01

    Full Text Available CONTEXT: The CDR-3 region of heavy-chain immunoglobulin has been used as a clonal marker in the study of minimal residual disease in children with acute lymphoblastic leukemia. Southern blot and polymerase chain reaction studies have demonstrated the occurrence of bi/oligoclonality in a variable number of cases of B-lineage acute lymphoblastic leukemia, a fact that may strongly interfere with the detection of minimal residual disease. Oligoclonality has also been associated with a poorer prognosis and a higher chance of relapse. OBJECTIVES: To correlate bi/oligoclonality, detected by polymerase chain reaction in Brazilian children with B-lineage acute lymphoblastic leukemia with a chance of relapse, with immunophenotype, risk group, and disease-free survival. DESIGN: Prospective study of patients’ outcome. SETTING: Pediatric Oncology Unit of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. PARTICIPANTS: 47 children with acute lymphoblastic leukemia DIAGNOSTIC TEST: Polymerase chain reaction using consensus primers for the CDR-3 region of heavy chain immunoglobulin (FR3A, LJH and VLJH for the detection of clonality. RESULTS: Bi/oligoclonality was detected in 15 patients (31.9%. There was no significant difference between the groups with monoclonality and biclonality in terms of the occurrence of a relapse (28.1% versus 26.1%, presence of CALLA+ (81.2% versus 80% or risk group (62.5% versus 60%. Disease-free survival was similar in both groups, with no significant difference (p: 0.7695. CONCLUSIONS: We conclude that bi/oligoclonality was not associated with the factors investigated in the present study and that its detection in 31.9% of the patients may be important for the study and monitoring of minimal residual disease.

  7. Evaluation of mRNA Expression Profile of ABCG2/BCRP in Childhood Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    M Entezar-e-Ghaem

    2013-12-01

    Conclusion: Results of this study showed no effect of ABCG2/BCRP expression level on MDR development in ALL. Accordingly, clinical value of ABCG2/BCRP expression profile determination was rejected as the prognosis value for childhood ALL in our geographical area.

  8. The metabolic syndrome in survivors of childhood acute lymphoblastic leukemia in Isfahan, Iran

    Science.gov (United States)

    Reisi, Nahid; Azhir, Afshin; Hashemipour, Mahin; Raeissi, Pouran; Amini, Abasgholi; Moafi, Alireza

    2009-01-01

    BACKGROUND: To determine the prevalence of metabolic syndrome in survivors of childhood leukemia in Isfahan, Iran. METHODS: During a 4-year period (2003 to 2007), 55 children (33 male and 22 female) diagnosed with ALL at Unit of Hematology/ Oncology, Department of Pediatrics, Isfahan University of Medical Science, were enrolled in this cross-sectional study. Metabolic syndrome was defined using the modified version of Adult Treatment Panel (ATP III) crite-ria. Insulin resistance was defined based on the homeostasis model assessment index (HOMA-IR). RESULTS: The mean age of participates was 10.4 years (range 6-19 years) and the mean interval since completion of chemotherapy was 35 months. Twenty percent (11/55) of survivors (10 male, 1 female) met criteria for diagnosis of metabolic syndrome. Obesity was observed in one forth of patients and nearly 3/4 of obese patients had metabolic syndrome. High serum insulin levels were found in 16% of participants and in 63% of obese survivors. The mean insulin levels in survivors with metabolic syndrome was three-times more than those without (28.3 mu/l vs. 9.57 mu/l, p = 0.004). Insulin resistance was detected in 72.7% of survivors with metabolic syndrome and it was positively correlated with serum triglycerides (0.543, p ≤ 0.001), systolic and diastolic BP (0.348, p = 0.01 and 0.368, p = 006 respectively), insulin levels (0.914, p < 0.001) and blood sugar (0.398, p = 003). CONCLUSIONS: The prevalence of metabolic syndrome in survivors of childhood leukemia in Iran is higher than developed countries. Nearly all of the obese patients had metabolic syndrome. Weight control and regular physical exercise are recommended to the survivors. PMID:21772869

  9. Garlic compounds selectively kill childhood pre-B acute lymphoblastic leukemia cells in vitro without reducing T-cell function: Potential therapeutic use in the treatment of ALL

    Directory of Open Access Journals (Sweden)

    Greg Hodge

    2008-03-01

    Full Text Available Greg Hodge1, Stephen Davis2, Michael Rice1, Heather Tapp1, Ben Saxon1, Tamas Revesz11Haematology/Oncology Department, Women’s and Children’s Hospital, North Adelaide, Australia; 2Department of Mycology, Women’s and Children’s Hospital, North Adelaide, AustraliaAbstract: Drugs used for remission induction therapy for childhood precursor-B acute lymphoblastic leukemia (ALL are nonselective for malignant cells. Several garlic compounds have been shown to induce apoptosis of cancer cells and to alter lymphocyte function. To investigate the effect of garlic on the apoptosis of ALL cells and lymphocyte immune function, cells from newly diagnosed childhood ALL patients were cultured with several commonly used chemotherapeutic agents and several garlic compounds. Apoptosis, lymphocyte proliferation and T-cell cytokine production were determined using multiparameter flow cytometry. At concentrations of garlic compounds that did not result in significant increases in Annexin V and 7-AAD staining of normal lymphocytes, there was a significant increase in apoptosis of ALL cells with no alteration of T-cell proliferation as determined by CD25/CD69 upregulation or interferonγ, interleukin-2 or tumor necrosis factor-α intracellular cytokine production. In contrast, the presence of chemotherapeutic agents resulted in nonselective increases in both lymphocyte and ALL apoptosis and a decrease in T-cell proliferation and cytokine production. In conclusion, we show selective apoptosis of malignant cells by garlic compounds that do not alter T-cell immune function and indicate the potential therapeutic benefit of garlic compounds in the treatment of childhood ALL.Keywords: childhood precursor-B acute lymphoblastic leukemia, garlic, apoptosis, immune function, intracellular cytokines

  10. Molecular detection of minimal residual disease is a strong predictive factor of relapse in childhood B-lineage acute lymphoblastic leukemia with medium risk features. A case control study of the International BFM study group

    NARCIS (Netherlands)

    Biondi, A; Valsecchi, MG; Seriu, T; D'Aniello, E; Willemse, MJ; Fasching, K; Pannunzio, A; Gadner, H; Schrappe, M; Kamps, WA; Bartram, CR; van Dongen, JJM; Panzer-Grumayer, ER

    2000-01-01

    The medium-risk B cell precursor acute lymphoblastic leukemia (ALL) accounts for 50-60% of total childhood ALL and comprises the largest number of relapses still unpredictable with diagnostic criteria. To evaluate the prognostic impact of minimal residual disease (MRD) in this specific group, a case

  11. Transformation of Myelodysplastic Syndrome to Acute Lymphoblastic Leukemia in a Child

    OpenAIRE

    2010-01-01

    Childhood myelodysplastic syndrome (MDS) is an uncommon condition. Unlike adult MDS, pediatric patients have a more progressive course and rapidly transform to acute myeloid leukemia. Evolution to acute lymphoblastic leukemia is extremely rare. We report a 5 year old female child who presented with refractory anemia with excess blasts and transformed into acute lymphoblastic leukemia 4 months after initial diagnosis.

  12. Randomized double blind trial of ciprofloxacin prophylaxis during induction treatment in childhood acute lymphoblastic leukemia in the WK-ALL protocol in Indonesia

    Directory of Open Access Journals (Sweden)

    Widjajanto PH

    2013-02-01

    Full Text Available Pudjo H Widjajanto,1 Sumadiono Sumadiono,1 Jacqueline Cloos,2,3 Ignatius Purwanto,1 Sutaryo Sutaryo,1 Anjo JP Veerman1,21Pediatric Hematology and Oncology Division, Department of Pediatrics, Dr Sardjito Hospital, Medical Faculty, Universitas Gadjah Mada, Yogyakarta, Indonesia; 2Pediatric Oncology/Hematology Division, Department of Pediatrics, 3Department of Hematology, VU University Medical Center, Amsterdam, The NetherlandsObjectives: Toxic death is a big problem in the treatment of childhood acute lymphoblastic leukemia (ALL, especially in low-income countries. Studies of ciprofloxacin as single agent prophylaxis vary widely in success rate. We conducted a double-blind, randomized study to test the effects of ciprofloxacin monotherapy as prophylaxis for sepsis and death in induction treatment of the Indonesian childhood ALL protocol.Methods: Patients were randomized to the ciprofloxacin arm (n = 58 and to the placebo arm (n = 52. Oral ciprofloxacin monotherapy or oral placebo was administered twice a day. All events during induction were recorded: toxic death, abandonment, resistant disease, and complete remission rate.Results: Of 110 patients enrolled in this study, 79 (71.8% achieved CR. In comparison to the placebo arm, the ciprofloxacin arm had lower nadir of absolute neutrophil count during induction with median of 62 (range: 5–884 versus 270 (range: 14–25,480 × 109 cells/L (P > 0.01, greater risks for experiencing fever (50.0% versus 32.7%, P = 0.07, clinical sepsis (50.0% versus 38.5%, P = 0.22, and death (18.9% versus 5.8%, P = 0.05.Conclusion: In our setting, a reduced intensity protocol in a low-income situation, the data warn against using ciprofloxacin prophylaxis during induction treatment. A lower nadir of neutrophil count and higher mortality were found in the ciprofloxacin group.Keywords: ciprofloxacin, prophylaxis, childhood acute lymphoblastic leukemia, randomized trial, low-income country

  13. Increased μ-Calpain Activity in Blasts of Common B-Precursor Childhood Acute Lymphoblastic Leukemia Correlates with Their Lower Susceptibility to Apoptosis.

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    Anna Mikosik

    Full Text Available Childhood acute lymphoblastic leukemia (ALL blasts are characterized by inhibited apoptosis promoting fast disease progress. It is known that in chronic lymphocytic and acute myeloid leukemias the reduced apoptosis is strongly related with the activity of calpain-calpastatin system (CCS composed of cytoplasmic proteases--calpains--performing the modulatory proteolysis of key proteins involved in cell proliferation and apoptosis, and of their endogenous inhibitor--calpastatin. Here, the CCS protein abundance and activity was for the first time studied in childhood ALL blasts and in control bone marrow CD19+ B cells by semi-quantitative flow cytometry and western blotting of calpastatin fragments resulting from endogenous calpain activity. Significantly higher μ-calpain (CAPN1 gene transcription, protein amounts and activity (but not those of m-calpain, with calpastatin amount and transcription of its gene (CAST greatly varying were observed in CD19(+ ALL blasts compared to control cells. Significant inverse relation between the amount/activity of calpain and spontaneous apoptosis was noted. Patients older than 10 years (considered at higher risk displayed increased amounts and activities of blast calpain. Finally, treatment of blasts with the tripeptide calpain inhibitors II and IV significantly and in dose-dependent fashion increased the percentage of blasts entering apoptosis. Together, these findings make the CCS a potential new predictive tool and therapeutic target in childhood ALL.

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

    Science.gov (United States)

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

    1993-01-01

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

  15. Efficacy and Toxicity of Intrathecal Liposomal Cytarabine in First-line Therapy of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Harila-Saari, Arja; Grell, Kathrine

    2016-01-01

    We investigated efficacy and toxicity of replacing conventional triple (cytarabine, methotrexate, and hydrocortisone) intrathecal therapy (TIT) with liposomal cytarabine during maintenance therapy among 40 acute lymphoblastic leukemia patients. Twenty-eight of 29 patients in the TIT arm received...... TIT and 9/11 in the liposomal cytarabine arm received liposomal cytarabine. Arachnoiditis occurred in all initial 5 patients given liposomal cytarabine and intrathecal prednisolone succinate. Subsequently liposomal cytarabine was given with systemic dexamethasone. Neurotoxicity occurred at 6....../27 liposomal cytarabine administrations with concomitant dexamethasone (22%). More liposomal cytarabine-treated patients experienced neurotoxicity in relation to intrathecal therapy during at least 1 cycle compared with TIT-treated patients (6/9 [67%] vs. 3/28 [11%], P=0.002). Apart from intermittent lower...

  16. Academic career after treatment for acute lymphoblastic leukaemia

    NARCIS (Netherlands)

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

    2000-01-01

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

  17. Therapy-Related Myelodysplastic Syndrome Following Treatment for Childhood Acute Lymphoblastic Leukemia: Outcome of Patients Registered in the EWOG-MDS 98/06 Studies

    DEFF Research Database (Denmark)

    Strahm, Birgitte; Amann, Roland; De Moerloose, Barbara

    Objective: Therapy-related myelodysplastic syndrome (tMDS) following treatment of childhood acute lymphoblastic leukemia (ALL) is one of the most frequently observed secondary malignancies in survivors of childhood cancer. Allogeneic stem cell transplantation (SCT) is the only curative treatment....... This analysis was performed to asses the outcome of patients with tMDS following treatment for childhood ALL reported to the EWOG-MDS study group. Patients and Transplant Procedure: Forty-three patients (19 male/24 female) were diagnosed with tMDS between August 1989 and August 2009. The median age at diagnosis...... was 8.9 yrs (3.4–20.5). The median interval from diagnosis of ALL to the diagnosis of tMDS was 3.3 yrs (1.7–7.0). Five patients did not receive SCT and died due to progressive disease at a median of 5.6 mo after diagnosis. Thirty-eight patients were transplanted. One patient was excluded from...

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

    Science.gov (United States)

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

    2013-07-01

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

  19. Using a Bayesian hierarchical model for identifying single nucleotide polymorphisms associated with childhood acute lymphoblastic leukemia risk in case-parent triads.

    Directory of Open Access Journals (Sweden)

    Ying Cao

    Full Text Available Childhood acute lymphoblastic leukemia (ALL is a condition that arises from complex etiologies. The absence of consistent environmental risk factors and the presence of modest familial associations suggest ALL is a complex trait with an underlying genetic component. The identification of genetic factors associated with disease is complicated by complex genetic covariance structures and multiple testing issues. Both issues can be resolved with appropriate Bayesian variable selection methods. The present study was undertaken to extend our hierarchical Bayesian model for case-parent triads to incorporate single nucleotide polymorphisms (SNPs and incorporate the biological grouping of SNPs within genes. Based on previous evidence that genetic variation in the folate metabolic pathway influences ALL risk, we evaluated 128 tagging SNPs in 16 folate metabolic genes among 118 ALL case-parent triads recruited from the Texas Children's Cancer Center (Houston, TX between 2003 and 2010. We used stochastic search gene suggestion (SSGS in hierarchical Bayesian models to evaluate the association between folate metabolic SNPs and ALL. Using Bayes factors among these variants in childhood ALL case-parent triads, two SNPs were identified with a Bayes factor greater than 1. There was evidence that the minor alleles of NOS3 rs3918186 (OR = 2.16; 95% CI: 1.51-3.15 and SLC19A1 rs1051266 (OR = 2.07; 95% CI: 1.25-3.46 were positively associated with childhood ALL. Our findings are suggestive of the role of inherited genetic variation in the folate metabolic pathway on childhood ALL risk, and they also suggest the utility of Bayesian variable selection methods in the context of case-parent triads for evaluating the role of SNPs on disease risk.

  20. Role of Electromagnetic Field Exposure in Childhood Acute Lymphoblastic Leukemia and No Impact of Urinary Alpha- Amylase--a Case Control Study in Tehran, Iran.

    Science.gov (United States)

    Tabrizi, Maral Mazloomi; Hosseini, Seyed Ahmad

    2015-01-01

    Childhood acute lymphoblastic leukemia (ALL) is one of the most common hematologic malignancies which accounts for one fourth of all childhood cancer cases. Exposure to environmental factors around the time of conception or pregnancy can increase the risk of ALL in the offspring. This study aimed to evaluate the influence of prenatal and postnatal exposure to high voltage power lines on the incidence of childhood ALL. It also examines the role of various factors such as environmental factors and alpha-amylase as a marker in the development of leukemia. This cross-sectional case control study was carried out on 22 cases and 100 controls who born and lived in low socioeconomic families in Tehran and were hospitalized for therapeutic purposes in different hospitals of rom 2013-2014. With regard to the underlying risk factors; familial history and parental factors were detected as risk factors of ALL but in this age, socioeconomic and zonal matched case control study, prenatal and childhood exposure to high voltage power lines was considered as the most important environmental risk factor (p=0.006, OR=3.651, CI 95% 1.692-7.878). As the population study was from low socioeconomic state, use of mobiles, computers and microwaves was negligible. Moreover prenatal and postnatal exposure to all indoor electrically charged objects were not detected as significant environmental factors in the present study. This work defined the risk of environmental especially continuous pre and postnatal exposure to high voltage power lines and living in pollutant regions through the parents or children as well as the previously described risk factors of ALL for the first time in low socioeconomic status Iranian population.

  1. Physical Activity in Long-term Survivors of Acute Lymphoblastic Leukemia in Childhood and Adolescence: A Cross-sectional Cohort Study.

    Science.gov (United States)

    Nayiager, Trishana; Barr, Ronald D; Anderson, Loretta; Cranston, Amy; Hay, John

    2017-01-01

    Inadequate physical activity (PA) and elevated overweight/obesity (OW/OB) rates are common in survivors of cancer in childhood, especially acute lymphoblastic leukemia (ALL). Bony morbidity, including fractures, is also prevalent among survivors of ALL. This study examined the interrelationships of PA, measured in hours by the Habitual Activity Estimation Scale; OW/OG, defined by body mass index; and fractures (yes/no) in survivors of ALL (n=75) more than 10 years after diagnosis. All had been treated using protocols of the Dana Farber Cancer Institute Childhood ALL Consortium. The median age was 21.15 years and time from diagnosis 15.07 years, and 27 subjects had experienced fractures. More than 30% of the total sample were OW/OB. There was no correlation of body mass index with present PA. There were no significant differences between those with/without fractures in terms of age, sex, time from diagnosis, and the prevalence of OW/OB. Subjects with fractures during treatment reported more total activity on typical weekend days than those without fractures (mean 8.8 vs. 6.9 h, P<0.01). There was no significant difference on weekdays. Higher activity on weekends suggests that fractures may have occurred more commonly in those who had a more active lifestyle before, during, and after treatment.

  2. The clinical importance of myeloid antigen coexpression and TEL-AML1 mutation in patients with childhood acute lymphoblastic leukemia

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    Ayşen Türedi Yıldırım

    2013-03-01

    Full Text Available Objective: In this study, we aim to investigate the relationship,if any, between clinical features, prognosis, and thecoexpressions and TEL-AML1 mutation in patients withacute lymphoblastic leukemia (ALL.Methods: Eigthy-three patients with acute lymphoblasticleukemia were retrospectively examined. Age, gender,White blood cell count, hemoglobin level, platelet count,ALL subtypei (B or T ALL, risk groups, surface antigensdeteceted by flow cytometry, existence of TEL-AML1 mutations,response, remission and relapse status at 8., 15.ve 33. Days of treatment were recorded and analyzed.Results: 15 (18% out of 83 were identified with aberrantantigen expression. Of these patients, twelve (14.4%had myeloid antigen coexpression (CD13 and/or CD33,two with B cell ALL had CD2 and CD7 coexpressions respectively,one with T cell ALL had CD19 coexpression.No significant differences were found between patientswith and without myeloid antigen coexpression in terms ofhemoglobin levels, white blood cells and platelet counts,responses given on the 8th, 15th, and 30th days on the treatment,risk groups, and relapse (p>0.05. Myeloid antigencoexpression was found in 4 of 13 patients who were identifiedwith TEL-AML1 mutation. No significant relationshipwas found between this mutation and coexpressions. Norelapse and exitus were observed in four patients with coexpressionand TEL-AML1.Conclusion: The prognosis and clinical features showsno statistically significant relationship with the presence ofneither Myeloid antigen expression nor TEL-AML1 mutation.We believe, however, the future studies involving biggersample sizes will prove to be useful in terms of moreconvincing results. J Clin Exp Invest 2013; 4(1: 90-94Key words: Acute lenfoblastic leukemia, coexpression,TEL-AML1 mutation, prognosis

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

    Science.gov (United States)

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

    1990-04-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    M Belayet Hossain

    2017-01-01

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

  6. Acute lymphoblastic leukemia presenting with gross hematuria

    OpenAIRE

    Kalbani, Naifain Al; Weitzman, Sheila; Abdelhaleem, Mohamed; Carcao, Manuel; Abla, Oussama

    2007-01-01

    A case of a six-year-old boy presenting with gross hematuria is reported. Investigations revealed the etiology of the hematuria to be thrombocytopenia in the setting of newly diagnosed acute lymphoblastic leukemia. The diagnosis of leukemia was confirmed by bone marrow examination. The patient’s hematuria completely resolved with platelet transfusions. Although thrombocytopenia is a very common presenting feature of acute lymphoblastic leukemia, gross hematuria is exceedingly rare. Thus, thro...

  7. Living near overhead high voltage transmission power lines as a risk factor for childhood acute lymphoblastic leukemia: a case-control study.

    Science.gov (United States)

    Sohrabi, Mohammad-Reza; Tarjoman, Termeh; Abadi, Alireza; Yavari, Parvin

    2010-01-01

    This study aimed to investigate association of living near high voltage power lines with occurrence of childhood acute lymphoblastic leukemia (ALL). Through a case-control study 300 children aged 1-18 years with confirmed ALL were selected from all referral teaching centers for cancer. They interviewed for history of living near overhead high voltage power lines during at least past two years and compared with 300 controls which were individually matched for sex and approximate age. Logistic regression, chi square and paired t-tests were used for analysis when appropriate. The case group were living significantly closer to power lines (Plines (Plines against more than 600 meters. This ratio estimated as 9.93 (95%CI: 3.47 to 28.5) for 123 KV, 10.78 (95%CI: 3.75 to 31) for 230 KV and 2.98 (95%CI: 0.93 to 9.54) for 400 KV lines. Odds of ALL decreased 0.61 for every 600 meters from the nearest power line. This study emphasizes that living close to high voltage power lines is a risk for ALL.

  8. Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1

    Directory of Open Access Journals (Sweden)

    Jessica Purizaca

    2013-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is the most frequent malignancy of childhood. Substantial progress on understanding the cell hierarchy within ALL bone marrow (BM has been recorded in the last few years, suggesting that both primitive cell fractions and committed lymphoid blasts with immature stem cell-like properties contain leukemia-initiating cells. Nevertheless, the biology of the early progenitors that initiate the lymphoid program remains elusive. The aim of the present study was to investigate the ability of lymphoid progenitors from B-cell precursor ALL BM to proliferate and undergo multilineage differentiation. By phenotype analyses, in vitro proliferation assays, and controlled culture systems, the lymphoid differentiation potentials were evaluated in BM primitive populations from B-cell precursor ALL pediatric patients. When compared to their normal counterparts, functional stem and progenitor cell contents were substantially reduced in ALL BM. Moreover, neither B nor NK or dendritic lymphoid-cell populations developed recurrently from highly purified ALL-lymphoid progenitors, and their proliferation and cell cycle status revealed limited proliferative capacity. Interestingly, a number of quiescence-associated transcription factors were elevated, including the transcriptional repressor Gfi-1, which was highly expressed in primitive CD34+ cells. Together, our findings reveal major functional defects in the primitive hematopoietic component of ALL BM. A possible contribution of high levels of Gfi-1 expression in the regulation of the stem/progenitor cell biology is suggested.

  9. Baicalein Triggers Mitochondria-Mediated Apoptosis and Enhances the Antileukemic Effect of Vincristine in Childhood Acute Lymphoblastic Leukemia CCRF-CEM Cells

    Directory of Open Access Journals (Sweden)

    Yun-Ju Chen

    2013-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL accounts for approximately 75% of childhood leukemia, and chemotherapy remains the mainstay therapy. Baicalein is an active flavonoid used in traditional Chinese medicine and has recently been found to have anticancer, anti-inflammatory, and antiallergic properties. This study aims to investigate the molecular apoptotic mechanisms of baicalein in CCRF-CEM leukemic cells and to evaluate the combined therapeutic efficacy of baicalein with several commonly used chemotherapeutic drugs in CCRF-CEM cells. Our results demonstrate that baicalein induces mitochondria-dependent cleavage of caspases-9 and -3 and PARP with concomitant decreases in IAP family proteins, survivin, and XIAP. Furthermore, our results present for the first time that baicalein triggers a convergence of the intrinsic and extrinsic apoptotic pathways via the death receptor-caspase 8-tBid signaling cascade in CCRF-CEM cells. In addition, we also present for the first time that the combination of baicalein and vincristine results in a synergistic therapeutic efficacy. Overall, this combination strategy is recommended for future clinical trials in the treatment of pediatric leukemia owing to baicalein’s beneficial effects in alleviating the vomiting, nausea, and skin rashes caused by chemotherapy.

  10. Lymphoid progenitor cells from childhood acute lymphoblastic leukemia are functionally deficient and express high levels of the transcriptional repressor Gfi-1.

    Science.gov (United States)

    Purizaca, Jessica; Contreras-Quiroz, Adriana; Dorantes-Acosta, Elisa; Vadillo, Eduardo; Arriaga-Pizano, Lourdes; Fuentes-Figueroa, Silvestre; Villagomez-Barragán, Horacio; Flores-Guzmán, Patricia; Alvarado-Moreno, Antonio; Mayani, Hector; Meza, Isaura; Hernandez, Rosaura; Huerta-Yepez, Sara; Pelayo, Rosana

    2013-01-01

    Acute lymphoblastic leukemia (ALL) is the most frequent malignancy of childhood. Substantial progress on understanding the cell hierarchy within ALL bone marrow (BM) has been recorded in the last few years, suggesting that both primitive cell fractions and committed lymphoid blasts with immature stem cell-like properties contain leukemia-initiating cells. Nevertheless, the biology of the early progenitors that initiate the lymphoid program remains elusive. The aim of the present study was to investigate the ability of lymphoid progenitors from B-cell precursor ALL BM to proliferate and undergo multilineage differentiation. By phenotype analyses, in vitro proliferation assays, and controlled culture systems, the lymphoid differentiation potentials were evaluated in BM primitive populations from B-cell precursor ALL pediatric patients. When compared to their normal counterparts, functional stem and progenitor cell contents were substantially reduced in ALL BM. Moreover, neither B nor NK or dendritic lymphoid-cell populations developed recurrently from highly purified ALL-lymphoid progenitors, and their proliferation and cell cycle status revealed limited proliferative capacity. Interestingly, a number of quiescence-associated transcription factors were elevated, including the transcriptional repressor Gfi-1, which was highly expressed in primitive CD34⁺ cells. Together, our findings reveal major functional defects in the primitive hematopoietic component of ALL BM. A possible contribution of high levels of Gfi-1 expression in the regulation of the stem/progenitor cell biology is suggested.

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

    Science.gov (United States)

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

    2014-01-01

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

  12. Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse

    Science.gov (United States)

    Riccheri, María C.; Nuñez, Myriam; Alfonso, Graciela; Gueron, Geraldine; De Siervi, Adriana; Vazquez, Elba; Cotignola, Javier

    2017-01-01

    The inclusion of genotype at Acute Lymphoblastic Leukemia (ALL) diagnosis as a genetic predictor of disease outcome is under constant study. However, results are inconclusive and seem to be population specific. We analyzed the predictive value of germline polymorphisms for childhood ALL relapse and survival. We retrospectively recruited 140 Argentine patients with de novo ALL. Genotypes were analyzed using PCR-RFLP (GSTP1 c.313A > G, MDR1 c.3435T > C, and MTHFR c.665C > T) and multiplex PCR (GSTT1 null, GSTM1 null). Patients with the GSTP1 c.313GG genotype had an increased risk for relapse in univariate (OR = 2.65, 95% CI = 1.03–6.82, p = 0.04) and multivariate (OR = 3.22, 95% CI = 1.17–8.83, p = 0.02) models. The combined genotype slightly increased risk for relapse in the univariate (OR = 2.82, 95% CI = 1.09–7.32, p = 0.03) and multivariate (OR = 2.98, 95% CI = 1.14–7.79, p = 0.03) models for patients with 2/3-risk-genotypes (GSTT1 null, GSTM1 null, GSTP1 c.313GG). The Recurrence-Free Survival (RFS) was shorter for GSTP1 c.313GG (p = 0.025) and 2/3-risk-genotypes (p = 0.021). GST polymorphisms increased the risk of relapse and RFS of patients with childhood ALL. The inclusion of these genetic markers in ALL treatment protocols might improve risk stratification and reduce the number of relapses and deaths. PMID:27058755

  13. Flow Cytometric DNA index, G-band Karyotyping, and Comparative Genomic Hybridization in Detection of High Hyperdiploidy in Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Nygaard, Ulrikka; Larsen, Jacob; Kristensen, Tim D;

    2006-01-01

    High hyperdiploid acute lymphoblastic leukemia in children is related to a good outcome. Because these patients may be stratified to a low-intensity treatment, we have investigated the sensitivity of flow cytometry (FCM), G-band karyotyping (GBK), and high-resolution comparative genomic hybridiza...

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

    NARCIS (Netherlands)

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

    2001-01-01

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

  15. Bcl-2 family members in childhood acute lymphoblastic leukemia : relationships with features at presentation, in vitro and in vivo drug response and long-term clinical outcome

    NARCIS (Netherlands)

    Salomons, GS; Smets, LA; Verwijs-Janssen, M; Hart, AAM; Haarman, EG; Kaspers, GJL; Van Wering, ER; Van Der Does-Van Den Berg, A; Kamps, WA

    1999-01-01

    We have found that, in addition to Bcl-2 and Bar, the expression levels of apoptosis inducers (Bad, Bak) and inhibitors (Bcl-x(L), Mcl-1) were highly variable in blasts from 78 children with newly diagnosed acute lymphoblastic leukemia (ALL). The patients were enrolled in the national study ALL-7 of

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  17. Effect of the histone deacetylase inhibitor depsipeptide on B-cell differentiation in both TEL-AML1-positive and negative childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Stams, Wendy A G; den Boer, Monique L; Beverloo, H Berna; Kazemier, Karin M; van Wering, Elisabeth R; Janka-Schaub, Gritta E; Pieters, Rob

    2005-12-01

    The fusion protein TEL-AML1 in t(12;21)+ acute lymphoblastic leukemia (ALL) recruits co-repressors and histone deacetylases (HDAC), which transrepress AML1 target genes. Normal bone marrow cells were more resistant to HDAC inhibitor FK228 induced cell killing than were cells from ALL patients with or without t(12;21). FK228 induced differentiation in ALL, irrespective of the presence of t(12;21).

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  19. Vitamin D and bone minerals status in the long-term survivors of childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Nahid Reisi

    2015-01-01

    Conclusions: ALL treatment is associated with the increase in prevalence of vitamin D insufficiency in the childhood ALL survivors and since the low vitamin D level potentially increases the risk of low bone density, subsequent malignancies, and cardiovascular disease in the survivors, close follow-up of such patients are highly recommended to prevent the stated complications.

  20. Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Al-Modhwahi, Ibrahim; Andersen, Mette Klarskov;

    2009-01-01

    acute myeloid leukemias or myelodysplastic syndromes had monosomy 7 (n = 7) or 7q deletions (n = 2). In Cox multivariate analysis, longer duration of oral 6-mercaptopurine (6MP)/methotrexate (MTX) maintenance therapy (P = .02; longest for standard-risk patients) and presence of high hyperdiploidy (P......Among 1614 children with acute lymphoblastic leukemia (ALL) treated with the Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL-92 protocol, 20 patients developed a second malignant neoplasm (SMN) with a cumulative risk of 1.6% at 12 years from the diagnosis of ALL. Nine of the 16...

  1. Oral methotrexate/6-mercaptopurine may be superior to a multidrug LSA2L2 Maintenance therapy for higher risk childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Heyman, Mats; Kristinsson, Jon;

    2009-01-01

    The importance of maintenance therapy for higher risk childhood acute lymphoblastic leukemia (ALL) is uncertain. Between 1992 and 2001 the Nordic Society for Pediatric Haematology/Oncology compared in a nonrandomized study conventional oral methotrexate (MTX)/6-mercaptopurine (6MP) maintenance th...... significance. These results indicate that oral MTX/6MP maintenance therapy administered after the first year of remission can improve the cure rates of children with T-lineage or with higher risk B-lineage ALL.......The importance of maintenance therapy for higher risk childhood acute lymphoblastic leukemia (ALL) is uncertain. Between 1992 and 2001 the Nordic Society for Pediatric Haematology/Oncology compared in a nonrandomized study conventional oral methotrexate (MTX)/6-mercaptopurine (6MP) maintenance...... therapy with a multidrug cyclic LSA2L2 regimen. 135 children with B-lineage ALL and a white blood count > or =50 x 10/L and 98 children with T-lineage ALL were included. Of the 234 patients, the 135 patients who received MTX/6MP maintenance therapy had a lower relapse risk than the 98 patients who...

  2. ARID5B, IKZF1 and non-genetic factors in the etiology of childhood acute lymphoblastic leukemia: the ESCALE study.

    Science.gov (United States)

    Rudant, Jérémie; Orsi, Laurent; Bonaventure, Audrey; Goujon-Bellec, Stéphanie; Baruchel, André; Petit, Arnaud; Bertrand, Yves; Nelken, Brigitte; Pasquet, Marlène; Michel, Gérard; Saumet, Laure; Chastagner, Pascal; Ducassou, Stéphane; Réguerre, Yves; Hémon, Denis; Clavel, Jacqueline

    2015-01-01

    Genome-wide association studies (GWAS) have identified that frequent polymorphisms in ARID5B and IKZF1, two genes involved in lymphoid differentiation, increase the risk of childhood acute lymphoblastic leukemia (ALL). These findings markedly modified the current field of research on the etiology of ALL. In this new context, the present exploratory study investigated the possible interactions between these at-risk alleles and the non-genetic suspected ALL risk factors that were of sufficient prevalence in the French ESCALE study: maternal use of home insecticides during pregnancy, preconception paternal smoking, and some proxies for early immune modulation, i.e. breastfeeding, history of common infections before age one year, and birth order. The analyses were based on 434 ALL cases and 442 controls of European origin, drawn from the nationwide population-based case-control study ESCALE. Information on non-genetic factors was obtained by standardized telephone interview. Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested, with the SNPs coded as counts of minor alleles (trend variable). Statistical interactions were observed between rs4132601 and maternal insecticide use (p = 0.012), breastfeeding p = 0.017) and repeated early common infections (p = 0.0070), with allelic odds ratios (OR) which were only increased among the children not exposed to insecticides (OR = 1.8, 95%CI: 1.3, 2.4), those who had been breastfed (OR = 1.8, 95%CI: 1.3, 2.5) and those who had had repeated early common infections (OR = 2.4, 95%CI: 1.5, 3.8). The allelic ORs were close to one among children exposed to insecticides, who had not been breastfed and who had had no or few common infections. Repeated early common infections interacted with rs10740055 (p = 0.018) in the case-only design. Further studies are needed to evaluate whether these observations of a modification of the effect of the at-risk alleles by non

  3. Roles of genetic polymorphisms in the folate pathway in childhood acute lymphoblastic leukemia evaluated by Bayesian relevance and effect size analysis.

    Directory of Open Access Journals (Sweden)

    Orsolya Lautner-Csorba

    Full Text Available In this study we investigated whether polymorphisms in the folate pathway influenced the risk of childhood acute lymphoblastic leukemia (ALL or the survival rate of the patients. For this we selected and genotyped 67 SNPs in 15 genes in the folate pathway in 543 children with ALL and 529 controls. The results were evaluated by gender adjusted logistic regression and by the Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA methods. Bayesian structure based odds ratios for the relevant variables and interactions were also calculated. Altogether 9 SNPs in 8 genes were associated with altered susceptibility to ALL. After correction for multiple testing, two associations remained significant. The genotype distribution of the MTHFD1 rs1076991 differed significantly between the ALL and control population. Analyzing the subtypes of the disease the GG genotype increased only the risk of B-cell ALL (p = 3.52×10(-4; OR = 2.00. The GG genotype of the rs3776455 SNP in the MTRR gene was associated with a significantly reduced risk to ALL (p = 1.21×10(-3; OR = 0.55, which resulted mainly from the reduced risk to B-cell and hyperdiploid-ALL. The TC genotype of the rs9909104 SNP in the SHMT1 gene was associated with a lower survival rate comparing it to the TT genotype (80.2% vs. 88.8%; p = 0.01. The BN-BMLA confirmed the main findings of the frequentist-based analysis and showed structural interactional maps and the probabilities of the different structural association types of the relevant SNPs especially in the hyperdiploid-ALL, involving additional SNPs in genes like TYMS, DHFR and GGH. We also investigated the statistical interactions and redundancies using structural model properties. These results gave further evidence that polymorphisms in the folate pathway could influence the ALL risk and the effectiveness of the therapy. It was also shown that in gene association studies the BN-BMLA could be a useful

  4. ARID5B, IKZF1 and non-genetic factors in the etiology of childhood acute lymphoblastic leukemia: the ESCALE study.

    Directory of Open Access Journals (Sweden)

    Jérémie Rudant

    Full Text Available Genome-wide association studies (GWAS have identified that frequent polymorphisms in ARID5B and IKZF1, two genes involved in lymphoid differentiation, increase the risk of childhood acute lymphoblastic leukemia (ALL. These findings markedly modified the current field of research on the etiology of ALL. In this new context, the present exploratory study investigated the possible interactions between these at-risk alleles and the non-genetic suspected ALL risk factors that were of sufficient prevalence in the French ESCALE study: maternal use of home insecticides during pregnancy, preconception paternal smoking, and some proxies for early immune modulation, i.e. breastfeeding, history of common infections before age one year, and birth order. The analyses were based on 434 ALL cases and 442 controls of European origin, drawn from the nationwide population-based case-control study ESCALE. Information on non-genetic factors was obtained by standardized telephone interview. Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested, with the SNPs coded as counts of minor alleles (trend variable. Statistical interactions were observed between rs4132601 and maternal insecticide use (p = 0.012, breastfeeding p = 0.017 and repeated early common infections (p = 0.0070, with allelic odds ratios (OR which were only increased among the children not exposed to insecticides (OR = 1.8, 95%CI: 1.3, 2.4, those who had been breastfed (OR = 1.8, 95%CI: 1.3, 2.5 and those who had had repeated early common infections (OR = 2.4, 95%CI: 1.5, 3.8. The allelic ORs were close to one among children exposed to insecticides, who had not been breastfed and who had had no or few common infections. Repeated early common infections interacted with rs10740055 (p = 0.018 in the case-only design. Further studies are needed to evaluate whether these observations of a modification of the effect of the at-risk alleles by

  5. ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype

    Science.gov (United States)

    Hirabayashi, Shinsuke; Ohki, Kentaro; Nakabayashi, Kazuhiko; Ichikawa, Hitoshi; Momozawa, Yukihide; Okamura, Kohji; Yaguchi, Akinori; Terada, Kazuki; Saito, Yuya; Yoshimi, Ai; Ogata-Kawata, Hiroko; Sakamoto, Hiromi; Kato, Motohiro; Fujimura, Junya; Hino, Moeko; Kinoshita, Akitoshi; Kakuda, Harumi; Kurosawa, Hidemitsu; Kato, Keisuke; Kajiwara, Ryosuke; Moriwaki, Koichi; Morimoto, Tsuyoshi; Nakamura, Kozue; Noguchi, Yasushi; Osumi, Tomoo; Sakashita, Kazuo; Takita, Junko; Yuza, Yuki; Matsuda, Koich; Yoshida, Teruhiko; Matsumoto, Kenji; Hata, Kenichiro; Kubo, Michiaki; Matsubara, Yoichi; Fukushima, Takashi; Koh, Katsuyoshi; Manabe, Atsushi; Ohara, Akira; Kiyokawa, Nobutaka

    2017-01-01

    Fusion genes involving ZNF384 have recently been identified in B-cell precursor acute lymphoblastic leukemia, and 7 fusion partners have been reported. We further characterized this type of fusion gene by whole transcriptome sequencing and/or polymerase chain reaction. In addition to previously reported genes, we identified BMP2K as a novel fusion partner for ZNF384. Including the EP300-ZNF384 that we reported recently, the total frequency of ZNF384-related fusion genes was 4.1% in 291 B-cell precursor acute lymphoblastic leukemia patients enrolled in a single clinical trial, and TCF3-ZNF384 was the most recurrent, with a frequency of 2.4%. The characteristic immunophenotype of weak CD10 and aberrant CD13 and/or CD33 expression was revealed to be a common feature of the leukemic cells harboring ZNF384-related fusion genes. The signature gene expression profile in TCF3-ZNF384-positive patients was enriched in hematopoietic stem cell features and related to that of EP300-ZNF384-positive patients, but was significantly distinct from that of TCF3-PBX1-positive and ZNF384-fusion-negative patients. However, clinical features of TCF3-ZNF384-positive patients are markedly different from those of EP300-ZNF384-positive patients, exhibiting higher cell counts and a younger age at presentation. TCF3-ZNF384-positive patients revealed a significantly poorer steroid response and a higher frequency of relapse, and the additional activating mutations in RAS signaling pathway genes were detected by whole exome analysis in some of the cases. Our observations indicate that ZNF384-related fusion genes consist of a distinct subgroup of B-cell precursor acute lymphoblastic leukemia with a characteristic immunophenotype, while the clinical features depend on the functional properties of individual fusion partners. PMID:27634205

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

    Directory of Open Access Journals (Sweden)

    Kadalagere Lakshmana Girish Babu

    2016-01-01

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

  7. SCENARIO OF ACUTE LYMPHOBLASTIC LEUKAEMIA IN GWALIOR REGION

    Directory of Open Access Journals (Sweden)

    Mangal

    2016-04-01

    Full Text Available BACKGROUND Leukaemia is the most prevalent childhood cancer and Acute Lymphoblastic Leukaemia (ALL constitutes about 75% of all cases. The most frequent presenting symptoms are fever, weight loss and pallor. Early diagnosis of this haematological malignancy can be helpful for prognosis of disease. AIMS AND OBJECTIVES The objectives of the present study were to assess frequency of presenting symptoms, laboratory data and prognostic factors in children with diagnosis of ALL. MATERIALS AND METHODS The present study (2014 was performed in the Department of Pathology of Gajra Raja Medical College, Gwalior, over a period of one year from October 2013 to September 2014. The blood samples were received from patients attending various Departments of Jayarogya Groups of Hospitals, a tertiary care hospital. RESULTS Out of the 37 cases diagnosed as Acute Lymphoblastic Leukaemia, 25 (67.57% were male and 12 (32.43% were female, (male:female ratio: 2.1:1; 43.35% of patients which comprises highest number of cases belonged to 11-20 years of age group. The most frequent presenting symptoms was fever (83.78% followed by weakness (70.27% and loss of appetite (27%, while most frequent presenting sign was pallor (86.48% followed by lymphadenopathy (67.57% and splenomegaly (48.65%. Complete blood cell count was abnormal in all of the patients and pancytopenia was detected in 10.81% of the patients. Of all the patients, 91.89% had abnormal White Blood Cell (WBC count at presentation with about 80% were presented with Leukocytosis. FAB L1 subtype was more common as compared to FAB L2 subtype. CONCLUSION In our study (2014, Acute Lymphoblastic Leukaemia was more prevalent in males than in females and more common in childhood than in adult. FAB L1 subtype was more common as compared to FAB L2 subtype.

  8. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system

    Science.gov (United States)

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M.; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M.

    2017-01-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro. CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06–27.17; odds ratio=6.86, 95% confidence interval, 1.86–25.26, respectively). CCR7 expression in the upper fourth quartile correlated with

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

    NARCIS (Netherlands)

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

    2015-01-01

    Osteonecrosis and decline of bone density are serious side effects during and after treatment of childhood acute lymphoblastic leukemia. It is unknown whether osteonecrosis and low bone density occur together in the same patients, or whether these two osteogenic side-effects can mutually influence e

  10. Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet); R. Pieters (Rob); E.-J.D. Wind (Ernst-Jan); J.H.J.M. Bessems (Gert); M.M. van den Heuvel-Eibrink (Marry)

    2014-01-01

    textabstractThere is no consensus regarding how to manage osteonecrosis in pediatric acute lymphoblastic leukemia patients. Therefore, we performed a quality assessment of the literature with the result of a search strategy using the MESH terms osteonecrosis, children, childhood cancer, surgery, bis

  11. Minimal residual disease diagnostics in acute lymphoblastic leukemia: Need for sensitive, fast, and standardized technologies

    NARCIS (Netherlands)

    J.J.M. van Dongen (Jacques); V.H.J. van der Velden (Vincent); M. Brüggemann (Monika); A. Orfao (Alberto)

    2015-01-01

    textabstractMonitoring of minimal residual disease (MRD) has become routine clinical practice in frontline treatment of virtually all childhood acute lymphoblastic leukemia (ALL) and in many adult ALL patients. MRD diagnostics has proven to be the strongest prognostic factor, allowing for risk group

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  13. Erroneous exchange of asparaginase forms in the treatment of acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Cheung, K.C.; Bemt, P.M. van den; Torringa, M.L.; Tamminga, R.Y.; Pieters, R.; Smet, P.A. de

    2011-01-01

    For the treatment of children with acute lymphoblastic leukemia (ALL), Dutch pediatric oncologists use the Dutch Childhood Oncology Group ALL 10 protocol. This protocol is complex, as it comprises many different drug regimens. One of the drugs is asparaginase which is available in different forms wi

  14. Erroneous Exchange of Asparaginase Forms in the Treatment of Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    Cheung, Ka-Chun; van den Bemt, Patricia M. L. A.; Torringa, Maarten L. J.; Tamminga, Rienk Y. J.; Pieters, Rob; de Smet, Peter A. G. M.

    2011-01-01

    For the treatment of children with acute lymphoblastic leukemia (ALL), Dutch pediatric oncologists use the Dutch Childhood Oncology Group ALL 10 protocol. This protocol is complex, as it comprises many different drug regimens. One of the drugs is asparaginase which is available in different forms wi

  15. Genornewide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells

    NARCIS (Netherlands)

    Tissing, Wirn J. E.; den Boer, Monique L.; Meijerink, Jules P. P.; Menezes, Renee X.; Swagemakers, Sigrid; van der Spek, Peter J.; Sallan, Stephen E.; Armstrong, Scott A.; Pieters, Rob

    2007-01-01

    Glucocorticoids are keystone drugs in the treatment of childhood acute lymphoblastic leukemia (ALL). To get more insight in signal transduction pathways involved in glucocorticoid-induced apoptosis, Affymetrix U133A GeneChips were used to identify transcriptionally regulated genes on 3 and 8 hours o

  16. Pneumocystis jiroveci pneumonia prophylaxis during maintenance therapy influences methotrexate/6-mercaptopurine dosing but not event-free survival for childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Shabaneh, Diana; Bohnstedt, Cathrine

    2012-01-01

    Trimethoprim-sulfamethoxazole (TMP/SMX) is used in children with acute lymphoblastic leukemia (ALL) to prevent Pneumocystis pneumonia (PCP). We explored to which extent TMP/SMX influenced methotrexate (MTX)/6-mercaptopurine (6MP) dosage, myelosuppression, and event-free survival (EFS) during.......06) were related to reduced EFS. ANC had no effect on EFS among TMP/SMX2–7 patients (P = 0.40) but did for TMP/SMXnever patients (P = 0.02). The difference in the effect on EFS between TMP/SMX2–7 and TMP/SMXnever patients was not significant (P = 0.46). EFS did not differ between TMP/SMX2–7 and TMP....../SMXnever patients (0.83 vs. 0.83; P = 0.82). These results suggest that TMP/SMX is effective in preventing PCP and may have an antileukemic effect. TMP/SMX should be given the entire duration of maintenance therapy...

  17. Relapse in childhood acute lymphoblastic leukemia after elective cessation of initial treatment: failure of subsequent treatment with cyclophosphamide, cytosine arabinoside, vincristine and prednisone (COAP).

    Science.gov (United States)

    Sallan, S E; Hitchcock-Bryan, S

    1981-01-01

    Although the majority of children with acute lymphoblastic leukemia (ALL) can electively stop treatment after 2 1/2-5 years of continuous disease-free remission, 20-25% of those patients relapse after discontinuation of therapy. We treated 15 patients whose disease recurred after stopping treatment. Fourteen of them attained complete remission, but the median duration of disease-free survival was only 11 months. In this population, the site of initial relapse, bone marrow or testicle, did not influence subsequent outcome. Patients who relapsed within six months of stopping initial therapy had shorter second remissions than those who relapsed after six months. We conclude that the combination chemotherapy utilized in this study was inadequate for the control of relapsed ALL. Future programs will have to use different drug combinations or bone marrow transplantation.

  18. CLINICOPATHOLOGICAL STUDY OF ACUTE LYMPHOBLASTIC LEUKEMIA - A MULTIPARAMETER STUDY

    Directory of Open Access Journals (Sweden)

    Jagannath

    2015-11-01

    Full Text Available BACKGROUND Acute Lymphoblastic Leukaemia (ALL, a malignancy of lymphoid lineage cells, has excellent prognosis in children. Leukemia is the most prevalent childhood cancer and Acute Lymphoblastic Leukemia (ALL constitutes 75% of all cases. The most frequent presenting symptoms are fever, weight loss and pallor. Early detection of clinical symptoms positively affects timely diagnosis. AIMS & OBJECTIVES The objectives of the present study were to assess frequency of presenting symptoms, laboratory data and prognostic factors in children with diagnosis of ALL. MATERIALS & METHODS The present study (2014 was performed in the hematology section of Department of Pathology of Gajra Raja Medical College, Gwalior over a period of 12 months from 1st October 2013 to 30th September 2014. This was a prospective study. The blood samples were received from various departments of Jayarogya hospital especially from the Pediatric and Medicine departments. RESULTS Out of the 37 cases diagnosed as Acute Lymphoblastic Leukemia, 25(67.57% were male and 12(32.43%, were female, (male:female ratio: 2.1:1. 43.35% of patients which comprises highest number of cases belonged to 11-20 years of age group. The most frequent presenting symptoms was fever (83.78% followed by weakness (70.27% and loss of appetite (27% while most frequent presenting sign was pallor (86.48% followed by lymphadenopathy (67.57% and splenomegaly (48.65%. Complete blood cell count was abnormal in all of the patients, and pancytopenia was detected in 10.81% of the patients. Of all the patients, 91.89% had abnormal white blood cell (WBC count at presentation, 10.81% had leucopenia and 80% had leucocytosis. FAB L1 subtype was more common as compared to FAB L2 subtype. CONCLUSION In our study (2014, Acute Lymphoblastic Leukemia was more prevalent in males than in females and more common in childhood than in adult. FAB L1 subtype was more common as compared to FAB L2 subtype.

  19. Epigenetic Modifications in Pediatric Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Michael James Burke

    2014-05-01

    Full Text Available Aberrant epigenetic modifications are well-recognized drivers for oncogenesis. Pediatric acute lymphoblastic leukemia (ALL is no exception and serves as a model toward the significant impact these heritable alterations can have in leukemogenesis. In this brief review, we will focus on the main aspects of epigenetics which control leukemogenesis in pediatric ALL, mainly DNA methylation, histone modification and microRNA alterations. As we continue to gain better understanding of the driving mechanisms for pediatric ALL at both diagnosis and relapse, therapeutic interventions directed toward these pathways and mechanisms can be harnessed and introduced into clinical trials for pediatric ALL.

  20. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia

    NARCIS (Netherlands)

    A. Sanjuan-Pla (Alejandra); C. Bueno (C.); C. Prieto (Cristina); P. Acha (Pamela); R.W. Stam (Ronald); R. Marschalek (Rolf); P. Menéndez (Pablo)

    2015-01-01

    textabstractInfant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinicalmanagement and survival (∼85-90%) of childhood B-ALL,

  1. Vincristine sulfate liposomal injection for acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Soosay Raj TA

    2013-11-01

    Full Text Available Trisha A Soosay Raj,1 Amanda M Smith,2 Andrew S Moore,1,21Royal Children's Hospital, Children's Health Queensland Hospital and Health Service, Brisbane, Queensland, Australia; 2Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, QLD, AustraliaAbstract: Vincristine (VCR is one of the most extensively used cytotoxic compounds in hemato-oncology. VCR is particularly important for the treatment of acute lymphoblastic leukemia (ALL, a disease that accounts for approximately one-third of all childhood cancer diagnoses. VCR's full therapeutic potential has been limited by dose-limiting neurotoxicity, classically resulting in autonomic and peripheral sensory–motor neuropathy. In the last decade, however, the discovery that liposomal encapsulation of chemotherapeutics can modulate the pharmacokinetic characteristics of a compound has stimulated much interest in liposomal VCR (vincristine sulfate liposomal injection [VSLI] formulations for the treatment of ALL and other hematological malignancies. Promising data from recent clinical trials investigating VSLI in adults with ALL resulted in US Food and Drug Administration approval for use in patients with Philadelphia chromosome (t[9;22]/BCR–ABL1 (Ph-negative (Ph- disease. Additional clinical trials of VSLI in adults and children with both Ph-positive (Ph+ and Ph- ALL are ongoing. Here we review the preclinical and clinical experience to date with VSLI for ALL.Keywords: vincristine sulfate liposomal injection, liposomes, sphingosomal vincristine, acute lymphoblastic leukemia, chemotherapy

  2. Infections During Induction Therapy of Protocol CCLG-2008 in Childhood Acute Lymphoblastic Leukemia: A Single-center Experience with 256 Cases in China

    Institute of Scientific and Technical Information of China (English)

    Si-Dan Li; Yong-Bing Chen; Zhi-Gang Li; Run-Hui Wu; Mao-Quan Qin; Xuan Zhou; Jin Jiang

    2015-01-01

    Background:Infections remain a major cause of therapy-associated morbidity and mortality in children with acute lymphoblastic leukemia (ALL).Methods:We retrospectively analyzed the medical charts of 256 children treated for ALL under the CCLG-2008 protocol in Beijing Children's Hospital.Results:There were 65 infectious complications in 50 patients during vincristine,daunorubicin,L-asparaginase and dexamethasone induction therapy,including microbiologically documented infections (n =12; 18.5%),clinically documented infections (n =23; 35.3%) and fever of unknown origin (n =30; 46.2%).Neutropenia was present in 83.1% of the infectious episodes.In all,most infections occurred around the 15t1h day of induction treatment (n =28),and no patients died of infection-associated complications.Conclusions:The infections in this study was independent of treatment response,minimal residual diseases at the end of induction therapy,gender,immunophenotype,infection at first visit,risk stratification at diagnosis,unfavorable karyotypes at diagnosis and morphologic type.The infection rate of CCLG-2008 induction therapy is low,and the outcome of patients is favorable.

  3. Prevalence of Gene Rearrangements in Mexican Children with Acute Lymphoblastic Leukemia: A Population Study—Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

    Directory of Open Access Journals (Sweden)

    Vilma Carolina Bekker-Méndez

    2014-01-01

    Full Text Available Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL. The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010–2012. A total of 282 bone marrow samples were obtained at each child’s diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7% patients. ETV6-RUNX1 was detected in 21 (7.4% patients, TCF3-PBX1 in 20 (7.1% patients, BCR-ABL1 in 5 (1.8% patients, and MLL rearrangements in 4 (1.4% patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children.

  4. Prevalence of Gene Rearrangements in Mexican Children with Acute Lymphoblastic Leukemia: A Population Study—Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

    Science.gov (United States)

    Bekker-Méndez, Vilma Carolina; Miranda-Peralta, Enrique; Núñez-Enríquez, Juan Carlos; Olarte-Carrillo, Irma; Guerra-Castillo, Francisco Xavier; Pompa-Mera, Ericka Nelly; Ocaña-Mondragón, Alicia; Bernáldez-Ríos, Roberto; Medina-Sanson, Aurora; Jiménez-Hernández, Elva; Amador-Sánchez, Raquel; Peñaloza-González, José Gabriel; de Diego Flores-Chapa, José; Fajardo-Gutiérrez, Arturo; Flores-Lujano, Janet; Rodríguez-Zepeda, María del Carmen; Dorantes-Acosta, Elisa María; Bolea-Murga, Victoria; Núñez-Villegas, Nancy; Velázquez-Aviña, Martha Margarita; Torres-Nava, José Refugio; Reyes-Zepeda, Nancy Carolina; González-Bonilla, Cesar; Mejía-Aranguré, Juan Manuel

    2014-01-01

    Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL). The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010–2012. A total of 282 bone marrow samples were obtained at each child's diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7%) patients. ETV6-RUNX1 was detected in 21 (7.4%) patients, TCF3-PBX1 in 20 (7.1%) patients, BCR-ABL1 in 5 (1.8%) patients, and MLL rearrangements in 4 (1.4%) patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children. PMID:25692130

  5. Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia.

    Science.gov (United States)

    Te Winkel, Mariël L; Pieters, Rob; Wind, Ernst-Jan D; Bessems, J H J M Gert; van den Heuvel-Eibrink, Marry M

    2014-03-01

    There is no consensus regarding how to manage osteonecrosis in pediatric acute lymphoblastic leukemia patients. Therefore, we performed a quality assessment of the literature with the result of a search strategy using the MESH terms osteonecrosis, children, childhood cancer, surgery, bisphosphonates, 6 hydroxymethyl-glutaryl CoA reductase inhibitors, anticoagulants and hyperbaric oxygen, and terms related to these MESH terms. A randomized controlled trial showed that osteonecrosis can be prevented by intermittent, instead of continuous, corticosteroid administration. The studies on interventions after onset of osteonecrosis were of low-quality evidence. Seven pediatric acute lymphoblastic leukemia studies described non-surgical interventions; bisphosphonates (n=5), hyperbaric oxygen therapy (n=1), or prostacyclin analogs (n=1). Safety and efficacy studies are lacking. Five studies focused on surgical interventions; none was of sufficient quality to draw definite conclusions. In conclusion, preventing osteonecrosis is feasible in a proportion of the pediatric acute lymphoblastic leukemia patients by discontinuous, instead of continuous, steroid scheduling. The questions as to how to treat childhood acute lymphoblastic leukemia patients with osteonecrosis cannot be answered as good-quality studies are lacking.

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

    Science.gov (United States)

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

    2002-07-15

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

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

    Directory of Open Access Journals (Sweden)

    Seema A Kembhavi

    2012-01-01

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

  8. Prognostic value of bone marrowhematogones in childhood B-lineage acute lymphoblastic leukemia%原血细胞对于儿童急性B淋巴细胞白血病预后判断的价值

    Institute of Scientific and Technical Information of China (English)

    王月芳; 江咏梅; 高举; 周平; 张鸽

    2016-01-01

    ObjectiveTo study the prognostic value of hematogones (HGs) for childhood B-lineage acute lymphoblastic leukemia (B-ALL) during consolidation chemotherapy.MethodsA retrospective analysis was conducted for 196 children with newly-diagnosed B-ALL. They were divided into high-risk group (n=55), intermediate-risk group (n=69), and low-risk group (n=72) by risk stratiifcation, and into complete remission group (n=165) and relapse group (n=31) by clinical outcome. The European BIOMED-1 standard lfow cytometry for minimal residual disease (MRD) was used to determine the number of HGs during consolidation chemotherapy. The Kaplan-Meier survival curve was used to assess event-free survival (EFS).ResultsThe high-risk group had a signiifcantly lower number of HGs than the intermediate-risk and low-risk groups (P1.0% (P1.0%组,差异有统计学意义(P<0.05)。结论HGs 可反映B-ALL化疗效果,可用于B-ALL患儿疗效及预后的监测。

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

    Directory of Open Access Journals (Sweden)

    Gulhadiye Avcu

    2016-03-01

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

  10. Bone Marrow Cells in Acute Lymphoblastic Leukemia Create a Proinflammatory Microenvironment Influencing Normal Hematopoietic Differentiation Fates

    OpenAIRE

    2015-01-01

    B-cell acute lymphoblastic leukemia (B-ALL) is a serious public health problem in the pediatric population worldwide, contributing to 85% of deaths from childhood cancers. Understanding the biology of the disease is crucial for its clinical management and the development of therapeutic strategies. In line with that observed in other malignancies, chronic inflammation may contribute to a tumor microenvironment resulting in the damage of normal processes, concomitant to development and maintena...

  11. Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

    Science.gov (United States)

    Cancela, Camila Silva Peres; Murao, Mitiko; Viana, Marcos Borato; de Oliveira, Benigna Maria

    2012-01-01

    Background Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. Methods This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. Results The estimated probabilities of overall survival and event free survival at 5 years were 69.5% (± 3.6%) and 58.8% (± 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis ≥ 50 x 109/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count 50 x 109/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia. PMID:23323068

  12. Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Camila Silva Peres Cancela

    2012-01-01

    Full Text Available BACKGROUND: Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. METHODS: This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99 treatment protocol. RESULTS: The estimated probabilities of overall survival and event free survival at 5 years were 69.5% ( 3.6% and 58.8% ( 4.0%, respectively. The cumulative incidence of central nervous system (isolated or combined relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis > 50 x 10(9/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count 50 x 10(9/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia.

  13. Acute lymphoblastic leukemia | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available on the Trial E.1 Medical condition or disease under investigation E.1.1Medical condition(s) being investigated Acute... lymphoblastic leukemia E.1.1.1Medical condition in easily understood language Acute lymphoblastic

  14. Human parvovirus B19 DNA is not detected in Guthrie cards from children who have developed acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Isa, Adiba; Priftakis, Peter; Broliden, Kristina;

    2004-01-01

    BACKGROUND: There has been much speculation about the cause of childhood acute lymphoblastic leukemia (ALL). It has been suggested, on the basis of findings in epidemiological studies, that ALL may be initiated by an in utero infection of the fetus. The human parvovirus B19 (B19) is etiologically...

  15. Treatment of adult acute lymphoblastic leukaemia.

    Science.gov (United States)

    Jacobs, P; Wood, L; Novitzky, N

    1990-01-01

    Eighty-five consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 24 years (range 10-69 years), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, Adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate and monthly intrathecal therapy, with drug intensification comprising either vincristine, Adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was obtained in 59 patients (69%) and only the French-American-British (FAB) L1 morphology was a significant predictive factor (P = 0.048). Twenty-three patients failed to achieve CR and of these 12 had primary drug resistance. Median follow-up is currently 260 weeks, median predicted survival of all patients is 58 weeks and for those who achieved CR it is 104 weeks. Median duration of CR is 70 weeks. Of the prognostic factors for survival, only FAB L1 subtype was significant. Bone marrow relapses occurred in 29 patients, and of these 9 (31%) achieved CR. There has been CNS relapse in two patients and both have died. Eleven patients continue in CR off therapy, with a median of 152 weeks. This regimen is effective, with acceptable toxicity, and a number of patients are potentially cured. The incidence of resistant and relapsing disease is an argument for further intensifying both induction and postinduction therapy.

  16. Clinical Utility of Sequential Minimal Residual Disease Measurements in the Context of Risk-based Therapy in Childhood Acute Lymphoblastic Leukemia: a Prospective Study

    Science.gov (United States)

    Pui, Ching-Hon; Pei, Deqing; Coustan-Smith, Elaine; Jeha, Sima; Cheng, Cheng; Bowman, W Paul; Sandlund, John T; Ribeiro, Raul C; Rubnitz, Jeffrey E; Inaba, Hiroto; Bhojwani, Deepa; Gruber, Tanja A; Leung, Wing H; Downing, James R; Evans, William E; Relling, Mary V; Campana, Dario

    2015-01-01

    Summary Background The level of minimal residual disease (MRD) during remission induction is the most important prognostic indicator in acute lymphoblastic leukemia (ALL). We determined the clinical significance of MRD in the context of a prospective clinical study in which sequential MRD measurements were used to guide treatment decisions. Methods Between 2000 and 2007, 498 evaluable patients with newly diagnosed ALL were enrolled in St. Jude Study XV. Risk of relapse was provisionally classified as low, standard or high according to presenting clinical and laboratory features. Final risk assignment to determine treatment intensity was based mainly on MRD levels measured on days 19 and 46 of remission induction, and on week 7 of continuation treatment. Additional MRD determinations were made on weeks 17, 48 and 120 (end of therapy). Findings Regardless of the provisional risk classification, 10-year event-free survival was significantly inferior for patients with MRD ≥1% on day 19 compared with that of patients having lower MRD levels: 69.2% (95% CI 49.6–82.4, n=36) versus 95.5% (91.7–97.5, n=244) (p<0.001) for the provisional low-risk group and 65.1% (50.7–76.2, n=56) versus 82.9% (75.6–88.2, n=142) (p=0.008) for the provisional standard-risk group. Twelve patients with provisional low-risk ALL and MRD ≥1% on day 19 but negative MRD (<0.01%) on day 46 were treated for standard-risk ALL and had a 10-year event-free survival of 88.9% (43.3–98.4). For the 244 provisional low-risk patients, an MRD level of <1% on day 19 predicted a superior outcome, regardless of the MRD level on day 46. Among provisional standard-risk patients with MRD <1% on day 19, the 15 with persistent MRD on day 46 tended to have an inferior 10-year event-free survival compared with the 126 lacking detectable MRD (72.7% [42.5–88.8] versus 84.0% [76.3–89.4], p=0.06) after receiving the same post-remission treatment for standard-risk ALL. Among patients attaining MRD

  17. Treatment of acute lymphoblastic leukaemia (ALL).

    Science.gov (United States)

    Jacobs, P; Wood, L

    1992-08-01

    Forty-six consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 23 years (range 14 to 64), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard central nervous system (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate, and monthly intrathecal chemotherapy, with drug intensification comprising either vincristine, adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was achieved in 36 patients (78%) and only the FAB L1 morphology was a significant predictive factor (Chi-squared = 3.91: p < 0.05). Eight of the 10 non-responders had significant drug resistance and 3 deaths were associated with marrow hypoplasia. Median follow-up is 52 months. Median duration of CR is 28 months, median survival of all patients is 16 months, and for those who achieved CR is 44 months. There was no difference between the two maintenance arms. Significant prognostic factors for survival are French-American-British (FAB) subtype, in which the L1 is better than L2 (p = 0.05), and age (p = 0.035). Nineteen patients have experienced medullary relapse and 7 (37%) achieved subsequent CR; this is durable in a single patient who underwent allogeneic bone marrow transplantation. Eight patients (17%) had CNS disease at diagnosis; 5 achieved CR and 1 is alive and disease-free at 65+ months. There has been 1 CNS relapse. These results demonstrate that prolonged remissions and survival can be achieved with this protocol and many patients possibly cured. The level of toxicity is acceptable and the pattern of induction failure indicates that a margin exists for intensifying chemotherapy and thereby possibly further improving results.

  18. Bone marrow ectopic expression of a non-coding RNA in childhood T-cell acute lymphoblastic leukemia with a novel t(2;11(q11.2;p15.1 translocation

    Directory of Open Access Journals (Sweden)

    Leszl Anna

    2008-10-01

    Full Text Available Abstract Chromosomal translocations play a crucial role in tumorigenesis, often resulting in the formation of chimeric genes or in gene deregulation through position effects. T-cell acute lymphoblastic leukemia (T-ALL is associated with a large number of such rearrangements. We report the ectopic expression of the 3' portion of EST DA926692 in the bone marrow of a childhood T-ALL case showing a t(2;11(q11.2;p15.1 translocation as the sole chromosome abnormality. The breakpoints, defined at the sequence level, mapped within HPS5 (Hermansky Pudlak syndrome 5 intron 1 at 11p15.1, and DA926692 exon 2 at 2q11.2. The translocation was accompanied by a submicroscopic inversion that brought the two genes into the same transcriptional orientation. No chimeric trancript was detected. Interestingly, Real-Time Quantitative (RQ-PCR detected, in the patient's bone marrow, expression of a 173 bp product corresponding to the 3' portion of DA926692. Samples from four T-ALL cases with a normal karyotype and normal bone marrow used as controls were negative. It might be speculated that the juxtaposition of this genomic segment to the CpG island located upstream HPS5 activated DA92669 expression. RQ-PCR analysis showed expression positivity in 6 of 23 human tissues examined. Bioinformatic analysis excluded that this small non-coding RNA is a precursor of micro-RNA, although it is conceivable that it has a different, yet unknown, functional role. To the best of our knowledge, this is the first report, in cancer, of the activation of a small non-coding RNA as a result of a chromosomal translocation.

  19. Vincristine sulfate liposomal injection for acute lymphoblastic leukemia.

    Science.gov (United States)

    Raj, Trisha A Soosay; Smith, Amanda M; Moore, Andrew S

    2013-01-01

    Vincristine (VCR) is one of the most extensively used cytotoxic compounds in hemato-oncology. VCR is particularly important for the treatment of acute lymphoblastic leukemia (ALL), a disease that accounts for approximately one-third of all childhood cancer diagnoses. VCR's full therapeutic potential has been limited by dose-limiting neurotoxicity, classically resulting in autonomic and peripheral sensory-motor neuropathy. In the last decade, however, the discovery that liposomal encapsulation of chemotherapeutics can modulate the pharmacokinetic characteristics of a compound has stimulated much interest in liposomal VCR (vincristine sulfate liposomal injection [VSLI]) formulations for the treatment of ALL and other hematological malignancies. Promising data from recent clinical trials investigating VSLI in adults with ALL resulted in US Food and Drug Administration approval for use in patients with Philadelphia chromosome (t[9;22]/BCR-ABL1) (Ph)-negative (Ph-) disease. Additional clinical trials of VSLI in adults and children with both Ph-positive (Ph+) and Ph- ALL are ongoing. Here we review the preclinical and clinical experience to date with VSLI for ALL.

  20. 儿童急性淋巴细胞白血病预防性血小板输注阈值探讨%The threshold analysis for prophylactic platelet transfusions in childhood acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    周令; 徐学聚; 李欢欢

    2013-01-01

    Objective To investigate the threshold for prophylactic platelet transfusions in childhood acute lymphoblastic leukemia(ALL).Methods To analyze platelet transfusions and bleeding condition during chemotherapy in our department in childhood with ALL.Results 1 10 cases of children with a total 385 cases platelet transfusions.No complication group platelet count < 5 × 109/L,given platelet transfusion,major clinical bleeding events increased,complication group platelet count < 5 × 109/L,the risk of clinical bleeding increased.Conclusions The platelet transfusions threshold of 5 × 109/L for stable ALL patients is safe during chemotherapy.The platelet transfusion trigger was increased to 10 × 109/L or even higher in certain clinical situations.%目的 探讨急性淋巴细胞性白血病患儿化疗过程中预防性血小板输注阈值.方法 分析郑州大学第一附属医院儿科2年间急性淋巴细胞白血病患儿化疗期间血小板输注及出血情况.结果 110例患儿共输注血小板385例次,无合并症组血小板计数<5×109/L时输注血小板,临床主要出血事件增加,有合并症组在血小板计数< 10×109/L时临床出血风险增加.结论 儿童急性淋巴细胞白血病化疗过程中,在患儿一般状态稳定情况下,血小板输注阈值定为5×109/L相对安全,有合并症时血小板输注阈值应为10×109/L或更高.

  1. Optimizing asparaginase therapy for acute lymphoblastic leukemia.

    Science.gov (United States)

    Rizzari, Carmelo; Conter, Valentino; Starý, Jan; Colombini, Antonella; Moericke, Anja; Schrappe, Martin

    2013-03-01

    Asparaginases are important agents used in the treatment of children with acute lymphoblastic leukemia (ALL). Three types of asparaginase are currently available: two are derived from Escherichia coli [native asparaginase and pegylated asparaginase (PEG-asparaginase)] and one from Erwinia chrysanthemi (crisantaspase). All three products share the same mechanism of action but have different pharmacokinetic properties, which do not make them easily interchangeable. Among the known toxicities and side-effects, allergic reactions and silent inactivation represent the most important limitations to the prolonged use of any asparaginase product, with associated reduced therapeutic effects and poorer outcomes. Routine real time monitoring can help to identify patients with silent inactivation and facilitate a switch to a different product to ensure continued depletion of asparagine, completion of the treatment schedule and maintenance of outcomes. However, the most appropriate second-line treatment is still a matter of debate. PEG-asparaginase has lower immunogenicity and a longer half-life than native Escherichia coli (E. coli) asparaginase, which makes it useful for both first-line and second-line use with a reduced number of doses. However, PEG-asparaginase displays cross-reactivity with native E. coli asparaginase that may harm its therapeutic effects. Crisantaspase does not display cross-reactivity to either of the E. coli-derived products, which has made crisantaspase the second-line treatment option in a number of recent protocols. As crisantaspase has a much shorter biological half-life than the E. coli-derived products, the appropriate dosage and administration schedule are of paramount importance in delivering treatment with this product. In the ongoing trial AIEOP-BFM ALL 2009 (Associazione Italiana Ematologia Oncologia Pediatrica - Berlin-Franklin-Munster), in which PEG-asparaginase is used first-line, one dose of PEG-asparaginase is substituted by seven doses

  2. Individualized toxicity-titrated 6-mercaptopurine increments during high-dose methotrexate consolidation treatment of lower risk childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Frandsen, Thomas Leth; Abrahamsson, Jonas; Lausen, Birgitte Frederiksen;

    2011-01-01

    This study explored the feasibility and toxicity of individualized toxicity-titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment with High-dose methotrexate (HDM) (5000 mg/m2, ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m2 per...

  3. Epigenetics in MLL-rearranged infant Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    D.J.P.M. Stumpel (Dominique)

    2012-01-01

    textabstractNowadays the cure rate for children diagnosed with acute lymphoblastic leukemia (ALL) has exceeded 80%. Although this is considered to be one of the major successes in pediatric oncology, the subgroup of patients that did not benefit from the improved therapeutic strategies should not be

  4. Bone histomorphometry in children with newly diagnosed acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Leeuw, JA; Koudstaal, J; Wiersema-Buist, J; Kamps, WA; Timens, W

    2003-01-01

    The objective of this study was to obtain insight into bone formation and resorption in children with newly diagnosed untreated acute lymphoblastic leukemia (ALL). In 23 consecutive children with ALL, a bone biopsy was taken from the crista iliaca posterior under ketamine anesthesia, together with t

  5. L-asparaginase treatment in acute lymphoblastic leukemia

    NARCIS (Netherlands)

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

    2011-01-01

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

  6. Acute lymphoblastic leukemia in children with Down syndrome

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  7. Acute hemiplegia in childhood

    Energy Technology Data Exchange (ETDEWEB)

    Okuno, Takehiko; Takao, Tatsuo; Itoh, Masatoshi; Konishi, Yukuo; Nakano, Shozo (Kyoto Univ. (Japan). Faculty of Medicine)

    1983-04-01

    The results of CT in 100 patients with acute hemiplegia in childhood are reported here. The etiology was various: 2 patients had infratentorial brain tumors, 56 had cerebral vascular diseases, 3 had head injuries, 16 had intracranial infectious diseases, one had postinfectious encephalomyelitis, one had multiple sclerosis, 2 had epilepsy, and the diagnosis of 19 were unknown. Eleven patients had a normal CT and a good prognosis. As for the type of onset, there were patients of type 1 with fever and 42 with convulsions and unconsciousness; those of type 2 with convulsions and unconsciousness were 12, and those of type 3 without fever and convulsions were 46. This classification is assumed to be useful, as the type of onset is characteristic of the etiology. Six patients were diagnosed correctly by repeated examinations, although the first CT did not reveal any remarkable findings. Capsular infarction, occlusion of the posterior cerebral artery in acute hemiplegia in childhood, abnormal findings of the internal capsule, thalamus, and midbrain in a patient with postinfectious encephalomyelitis, and a diffuse low density in the CT of the unilateral hemisphere in the patients with acute encephalopathy and acute hemiplegia of an obscure origin have been found after the introduction of computerized tomography.

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

    Science.gov (United States)

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

    2015-12-01

    Osteonecrosis and decline of bone density are serious side effects during and after treatment of childhood acute lymphoblastic leukemia. It is unknown whether osteonecrosis and low bone density occur together in the same patients, or whether these two osteogenic side-effects can mutually influence each other's development. Bone density and the incidence of symptomatic osteonecrosis were prospectively assessed in a national cohort of 466 patients with acute lymphoblastic leukemia (4-18 years of age) who were treated according to the dexamethasone-based Dutch Child Oncology Group-ALL9 protocol. Bone mineral density of the lumbar spine (BMDLS) (n=466) and of the total body (BMDTB) (n=106) was measured by dual X-ray absorptiometry. Bone density was expressed as age- and gender-matched standard deviation scores. Thirty patients (6.4%) suffered from symptomatic osteonecrosis. At baseline, BMDLS and BMDTB did not differ between patients who did or did not develop osteonecrosis. At cessation of treatment, patients with osteonecrosis had lower mean BMDLS and BMDTB than patients without osteonecrosis (respectively, with osteonecrosis: -2.16 versus without osteonecrosis: -1.21, Posteonecrosis: -1.73 versus without osteonecrosis: -0.57, Posteonecrosis had steeper BMDLS and BMDTB declines during follow-up than patients without osteonecrosis (interaction group time, Posteonecrosis. Bone density declines from the time that osteonecrosis is diagnosed; this suggests that the already existing decrease in bone density during acute lymphoblastic leukemia therapy is further aggravated by factors such as restriction of weight-bearing activities and destruction of bone architecture due to osteonecrosis. Osteonecrosis can, therefore, be considered a risk factor for low bone density in children with acute lymphoblastic leukemia.

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

    Science.gov (United States)

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

    1997-02-01

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

  10. PEG-asparaginase allergy in children with acute lymphoblastic leukemia in the NOPHO ALL2008 protocol

    DEFF Research Database (Denmark)

    Henriksen, Louise Tram; Harila-Saari, Arja; Ruud, Ellen;

    2015-01-01

    BACKGROUND: L-Asparaginase is an effective drug in the treatment of childhood acute lymphoblastic leukemia (ALL). The use of L-asparaginase may be limited by serious adverse events of which allergy is the most frequent. The objective of this study was to describe the clinical aspects of PEG......-asparaginase allergy in children treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol. PROCEDURE: Children (1-17 years) enrolled in the NOPHO ALL2008 protocol between July 2008 and August 2011, who developed PEG-asparaginase allergy were identified through the NOPHO...

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

    Science.gov (United States)

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

    1989-01-01

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

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

    Science.gov (United States)

    2015-10-29

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

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

    Institute of Scientific and Technical Information of China (English)

    Philippe; Kastner; Susan; Chan

    2011-01-01

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

  14. Higher frequencies of chromosomal aberrations in lymphocytes of children with acute lymphoblastic leukemia after in vitro gamma irradiation

    Directory of Open Access Journals (Sweden)

    A Ramyar

    2012-12-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common malignancy in childhood, characterized by excess lymphoblasts, and immature white blood cells that are continuously multiplying and overproducing in the bone marrow. The aim of this investigation was to measure the sensitivity of lymphocytes against gamma irradiation in patients with acute lymphoblastic leukemia, and also find out the effect of such irradiations in causing chromosomal abnormalities.Methods: In this investigation performed between April 2010 and July 2011, at the Department of Genetics, Cancer Institute of Iran, we studied the effects of gamma irradiation on the lymphocytes of 20 children with acute lymphoblastic leukemia. The lymphocytes of 30 healthy donors were used to establish as a normal response to gamma irradiation and seven age-matched ataxia telangiectasia patients were recruited as positive control. The chromosomal radiosensitivity was assessed with the G2- and the G0-assay. We compared the mean number of chromosomal abnormalities such as chromosome and chromatid breakages, chromosome and chromatid gaps, and chromatid exchanges in one-hundred metaphases of patients and control groups.Results: The frequency of chromosomal aberrations was statistically higher among patients with acute lymphoblastic leukemia than the normal controls (P<0.01. In total, 65% of the patients were sensitive to gamma irradiation, but the remaining 35% were similar to the normal controls. Patients with ataxia telangiectasia showed the highest sensitivity to gamma irradiation (P=0.001.Conclusion: Our results showed that a high percentage of patients with acute lymphoblastic leukemia were sensitive to irradiation, meaning that maximum care should be taken during their treatment to avoid unnecessary X-rays or radiotherapies.

  15. Vincristine sulfate liposomal injection for acute lymphoblastic leukemia

    OpenAIRE

    Soosay Raj TA; Smith AM; Moore AS

    2013-01-01

    Trisha A Soosay Raj,1 Amanda M Smith,2 Andrew S Moore,1,21Royal Children's Hospital, Children's Health Queensland Hospital and Health Service, Brisbane, Queensland, Australia; 2Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, QLD, AustraliaAbstract: Vincristine (VCR) is one of the most extensively used cytotoxic compounds in hemato-oncology. VCR is particularly important for the treatment of acute lymphoblastic leukemia (ALL), a...

  16. Acute lymphoblastic leukemia presenting with a uterine cervical mass

    Directory of Open Access Journals (Sweden)

    N Geetha

    2015-01-01

    Full Text Available Involvement of female genital tract with acute lymphoblastic leukemia (ALL is extremely rare, and it is even rarer for a patient to have symptomatic presentation. We report the case of a middle-aged lady with ALL, who presented with severe abnormal uterine bleeding and a uterine cervical mass. Biopsy of the cervical mass showed infiltration by leukemic blasts. She received chemotherapy with Berlin-Frankfurt-Munster protocol and is alive in remission after 10 years.

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

    Directory of Open Access Journals (Sweden)

    Mina Islambulchilar

    2015-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Lohit Kumar Kalita

    2015-05-01

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

  19. Acute Lymphoblastic Leukemia Presented as Multiple Breast Masses

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-10-15

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

  20. Esophageal strictures during treatment for acute lymphoblastic leukemia.

    LENUS (Irish Health Repository)

    Kelly, Kevin

    2012-02-01

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

  1. The negative impact of being underweight and weight loss on survival of children with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    den Hoed, Marissa A. H.; Pluijm, Saskia M. F.; de Groot-Kruseman, Hester A.; te Winkel, Mariel L.; Fiocco, Martha; van den Akker, Erica L. T.; Hoogerbrugge, Peter; van den Berg, Henk; Leeuw, Jan A.; Bruin, Marrie C. A.; Bresters, Dorine; Veerman, Anjo J. P.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2015-01-01

    Body mass index and change in body mass index during treatment may influence treatment outcome of pediatric patients with acute lymphoblastic leukemia. However, previous studies in pediatric acute lymphoblastic leukemia reported contradictory results. We prospectively collected data on body composit

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

    NARCIS (Netherlands)

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

    2003-01-01

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

  3. General Information about Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... available from the NCI website . Chimeric antigen receptor (CAR) T-cell therapy CAR T-cell therapy is ... of Health FOLLOW US Facebook Twitter Instagram YouTube Google+ LinkedIn GovDelivery RSS CONTACT INFORMATION Contact Us LiveHelp ...

  4. Treatment Option Overview (Childhood Acute Lymphoblastic Leukemia)

    Science.gov (United States)

    ... available from the NCI website . Chimeric antigen receptor (CAR) T-cell therapy CAR T-cell therapy is ... of Health FOLLOW US Facebook Twitter Instagram YouTube Google+ LinkedIn GovDelivery RSS CONTACT INFORMATION Contact Us LiveHelp ...

  5. Risk Groups for Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... available from the NCI website . Chimeric antigen receptor (CAR) T-cell therapy CAR T-cell therapy is ... of Health FOLLOW US Facebook Twitter Instagram YouTube Google+ LinkedIn GovDelivery RSS CONTACT INFORMATION Contact Us LiveHelp ...

  6. Childhood acute lymphoblastic leukaemia and birthweight

    DEFF Research Database (Denmark)

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

    2013-01-01

    -control studies ever conducted. METHODS: Birthweight and gestational age on 4075 children with ALL and 12,065 controls were collected during the course of three studies conducted in the USA, the UK and Germany in the 1990s. Information was obtained from mothers at interview, and the impact of bias was evaluated...

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

    Directory of Open Access Journals (Sweden)

    Laura B Ramsey

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

  8. Acute Lymphoblastic Leukemia | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available estigation E.1.1Medical condition(s) being investigated Acute Lymphoblastic Leukemia E.1.1.1Medical conditio...E.1.2Version 18.0 E.1.2Level LLT E.1.2Classification code 10000845 E.1.2Term Acute lymphoblastic leukemia E.

  9. Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia.

    Directory of Open Access Journals (Sweden)

    Sabine Topka

    2015-06-01

    Full Text Available Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL, the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline ETV6 p. L349P mutation in a kindred affected by thrombocytopenia and ALL. A second ETV6 p. N385fs mutation was identified in an unrelated kindred characterized by thrombocytopenia, ALL and secondary myelodysplasia/acute myeloid leukemia. Leukemic cells from the proband in the second kindred showed deletion of wild type ETV6 with retention of the ETV6 p. N385fs. Enforced expression of the ETV6 mutants revealed normal transcript and protein levels, but impaired nuclear localization. Accordingly, these mutants exhibited significantly reduced ability to regulate the transcription of ETV6 target genes. Our findings highlight a novel role for ETV6 in leukemia predisposition.

  10. Purification and characterization of fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA)

    DEFF Research Database (Denmark)

    Hokland, P; Rosenthal, P; Griffin, J D

    1983-01-01

    Fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA) were purified from both fetal liver and fetal bone marrow by immune rosetting with sheep erythrocytes coated with rabbit anti-mouse immunoglobulin and by fluorescence-activated cell sorting. Dual...... antigen. Furthermore, using methanol-fixed cells, it could be shown that approximately 20% contained intracytoplasmic mu chains (cyto-mu) and that approximately 15% were positive for the terminal transferase enzyme (TdT) marker. The CALLA+ fetal cells thus closely resemble the childhood acute...... that these cells are relatively immature lymphoid cells, CALLA+ cells do not appear to contain either myeloid precursor cells (CFU-G/M) or the earliest lymphoid stem cells. Udgivelsesdato: 1983-Jan-1...

  11. Testis Scintigraphy in a Patient with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Mine Şencan Eren

    2014-02-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a pediatric malignancy associated with remissions and relapses. Common relapsing sitesare meninges, testis and ovary. Testicular scintigraphy is a highly specific modality used mainly in the differential diagnosis of testicular torsion and epidydimitis/epidydimo-orchitis. There is only one interesting image on leukemic infiltration with scrotal scintigraphy in the literature. The aim of this case presentation is to report that although the scintigraphic appearance of testicular torsion was observed in a patient with the diagnosis of ALL, testicular ALL infiltration was revealed in pathologic examination.

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

    Directory of Open Access Journals (Sweden)

    John Biju

    2009-12-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Studies on twins with concordant acute lymphoblastic leukemia (ALL) have revealed that ETV6-RUNX1 gene fusion is a common, prenatal genetic event with other driver aberrations occurring subclonally and probably postnatally. The fetal cell type that is transformed by ETV6-RUNX1 is not identified...... by such studies or by the analysis of early B-cell lineage phenotype of derived progeny. Ongoing, clonal immunoglobulin (IG) and cross-lineage T-cell receptor (TCR) gene rearrangements are features of B-cell precursor leukemia and commence at the pro-B-cell stage of normal B-cell lineage development. We reasoned...

  15. CDX2 gene expression in acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Hanaa H. Arnaoaut

    2014-06-01

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

  16. BMS-214662 in Treating Patients With Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myeloid Leukemia

    Science.gov (United States)

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Shiek Aejaz Aziz

    2015-01-01

    Full Text Available 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 patients of all age groups were enrolled for the study, of which flow cytometry was done in 144 patients. Statistical Analysis Used: Analysis was done using the variables on SPSS (statistical package for social sciences software on computer. Survival curves were estimated by method of Kaplan-Meir. Results: Majority of the patients were of B-cell (68.1% and 30.6% patients were of T-cell lineage. Of these, 80.6% patients were having cALLa positivity. Complete remission (CR was achieved in 59.1%, 16.4% relapsed, and 20.1% patients died. Conclusions: Phenotyping has become an important and integral part of diagnosis, classification, management and prognosticating in ALL. B-cell has been found to have a better survival over T-cell lymphoblastic leukemia. cALLa antigen positivity has good impact in achieving CR in only B-cell lineage, myeloid coexpression has no significant effect on the outcome. BFM (Berlin-Frankfurt-Münster based protocols though showed a higher CR and survival vis-a-vis UKALL-XII. However, patients enrolled in former group being of low risk category and lesser in numbers cannot be compared statistically with a fair degree of confidence.

  19. mRNA overexpression of BAALC: A novel prognostic factor for pediatric acute lymphoblastic leukemia

    Science.gov (United States)

    AZIZI, ZAHRA; RAHGOZAR, SOHEILA; MOAFI, ALIREZA; DABAGHI, MOHAMMAD; NADIMI, MOTAHAREH

    2015-01-01

    BAALC is a novel molecular marker in leukemia that is highly expressed in patients with acute leukemia. Increased expression levels of BAALC are known as poor prognostic factors in adult acute myeloid and lymphoid leukemia. The purpose of the present study was to evaluate the prognostic significance of the BAALC gene expression levels in pediatric acute lymphoblastic leukemia (ALL) and its association with MDR1. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the mRNA expression levels of BAALC and MRD1 were measured in bone marrow samples of 28 new diagnosed childhood ALL patients and 13 children without cancer. Minimal residual disease (MRD) was measured one year after the initiation of the chemotherapy using the RT-qPCR method. The high level expression of BAALC had a significant association with the pre-B-ALL subtype, leukocytosis and positive MRD after one year of treatment in leukemic patients. In addition, a positive correlation between BAALC and MDR1 mRNA expression was shown in this group. In conclusion, to the best of our knowledge, the increase of BAALC expression as a poor prognostic factor for childhood ALL is shown for the first time. Additionally, the correlation between BAALC and MDR1 in mRNA expression levels can aid for an improved understanding of the mechanism through which BAALC may function in ALL and multidrug resistance. PMID:26137238

  20. mRNA overexpression of BAALC: A novel prognostic factor for pediatric acute lymphoblastic leukemia.

    Science.gov (United States)

    Azizi, Zahra; Rahgozar, Soheila; Moafi, Alireza; Dabaghi, Mohammad; Nadimi, Motahareh

    2015-05-01

    BAALC is a novel molecular marker in leukemia that is highly expressed in patients with acute leukemia. Increased expression levels of BAALC are known as poor prognostic factors in adult acute myeloid and lymphoid leukemia. The purpose of the present study was to evaluate the prognostic significance of the BAALC gene expression levels in pediatric acute lymphoblastic leukemia (ALL) and its association with MDR1. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the mRNA expression levels of BAALC and MRD1 were measured in bone marrow samples of 28 new diagnosed childhood ALL patients and 13 children without cancer. Minimal residual disease (MRD) was measured one year after the initiation of the chemotherapy using the RT-qPCR method. The high level expression of BAALC had a significant association with the pre-B-ALL subtype, leukocytosis and positive MRD after one year of treatment in leukemic patients. In addition, a positive correlation between BAALC and MDR1 mRNA expression was shown in this group. In conclusion, to the best of our knowledge, the increase of BAALC expression as a poor prognostic factor for childhood ALL is shown for the first time. Additionally, the correlation between BAALC and MDR1 in mRNA expression levels can aid for an improved understanding of the mechanism through which BAALC may function in ALL and multidrug resistance.

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

    Directory of Open Access Journals (Sweden)

    Dania Lizet Quintanilla-Flores

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Stanley Cohan MD, PhD

    2015-03-01

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

  3. Bone Marrow Cells in Acute Lymphoblastic Leukemia Create a Proinflammatory Microenvironment Influencing Normal Hematopoietic Differentiation Fates

    Directory of Open Access Journals (Sweden)

    Armando Vilchis-Ordoñez

    2015-01-01

    Full Text Available B-cell acute lymphoblastic leukemia (B-ALL is a serious public health problem in the pediatric population worldwide, contributing to 85% of deaths from childhood cancers. Understanding the biology of the disease is crucial for its clinical management and the development of therapeutic strategies. In line with that observed in other malignancies, chronic inflammation may contribute to a tumor microenvironment resulting in the damage of normal processes, concomitant to development and maintenance of neoplastic cells. We report here that hematopoietic cells from bone marrow B-ALL have the ability to produce proinflammatory and growth factors, including TNFα, IL-1β, IL-12, and GM-CSF that stimulate proliferation and differentiation of normal stem and progenitor cells. Our findings suggest an apparently distinct CD13+CD33+ population of leukemic cells contributing to a proinflammatory microenvironment that may be detrimental to long-term normal hematopoiesis within B-ALL bone marrow.

  4. Subdural hemorrhages in acute lymphoblastic leukemia: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Rui Yin; CaiXia Qiu; XiaoHui Dong; YeLong Chen

    2016-01-01

    Background:Acute lymphoblastic leukemia is a rare hematological malignancy.Pure subdural hemorrhages in a patient with acute lymphoblastic leukemia patient are extremely rare.Case presentation:This case presented acute spontaneous subdural hemorrhage without head trauma at first,and acute lymphoblastic leukemia was diagnosed later.The second time,the patient was admitted with multiple pure subdural hemorrhages in different locations and periods with a history of slight head trauma.Conclusions:Pure subdural hemorrhages can occur in a patient with acute lymphoblastic leukemia.More care would be needed for pure subdural hemorrhages without obvious head trauma,and patients with hematological malignancies should be protected from even mild head trauma.

  5. A single high dose of idarubicin combined with high-dose ARA-C for treatment of first relapse in childhood 'high-risk' acute lymphoblastic leukaemia: a study of the AIEOP group.

    Science.gov (United States)

    Testi, Anna Maria; Del Giudice, Ilaria; Arcese, William; Moleti, Maria Luisa; Giona, Fiorina; Basso, Giuseppe; Biondi, Andrea; Conter, Valentino; Messina, Chiara; Rondelli, Roberto; Micozzi, Alessandra; Micalizzi, Concetta; Barisone, Elena; Locatelli, Franco; Dini, Giorgio; Aricò, Maurizio; Casale, Fiorina; Comis, Margherita; Ladogana, Saverio; Lippi, Alma; Mura, Rossella; Pinta, Marie France; Santoro, Nicola; Valsecchi, Maria Grazia; Masera, Giuseppe; Mandelli, Franco

    2002-09-01

    The outcome of children with acute lymphoblastic leukaemia (ALL) and early relapse remains unsatisfactory. In January 1995, the AIEOP (Associazione Italiana di Oncologia ed Ematologia Pediatrica) group opened a trial for children with ALL in first isolated or combined bone marrow relapse defined at high risk according to the length of first remission and the immunophenotype. The treatment plan included the combination of a single high-dose idarubicin and high-dose cytarabine as induction therapy followed by an intensive consolidation and stem cell transplant (SCT). In total, 100 children from 16 Italian centres were enrolled; 80 out of the 99 evaluable patients (81%) achieved second complete remission; eight (8%) died during induction and 11 (11%) failed to respond. A total of 42 out of the 80 responders (52.5%) received a SCT: 19 from an identical sibling, 11 from a matched unrelated donor and 12 from umbilical cord blood cells. The estimated 4-year overall survival and event-free survival were 25% and 21% respectively. Disease-free survival at 4 years was 25.8% for the 80 responders. At 4 years, 39 out of 100 children remain alive, with 27 of them free of leukaemia. This induction therapy has shown antileukaemic efficacy with acceptable toxicity; moreover, all responders proved eligible for intensive consolidation.

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  7. Genetic Polymorphisms Analysis of Glutathione S-transferase M1 and T1 in Children with Acute Lymphoblastic Leukemia

    Institute of Scientific and Technical Information of China (English)

    王军; 张利; 冯建飞; 王宏; 朱绍先; 胡豫; 李玉香

    2004-01-01

    Summary: The relationship between glutathione S-transferases (GSTs) M1, T1 genotype and childhood acute lymphoblastic leukemia (ALL) was investigated. GSTM1 and GSTT1 genotypes in genomic DNA from 67 children with ALL and 146 healthy controls were analyzed by using the multiplex polymerase chain reaction (PCR). The frequencies of GSTM1, M1-T1 null genotypes in ALL children were significantly higher than in the healthy controls (76.12 % versus 52.74 %, OR=2.856, P<0.001;50. 74 % versus 24. 66 %, OR=3. 148, P<0.001, respectively). However,there was no significant relationship between GSTT1 null genotype and ALL of children (61.19 %versus 49.32 %, OR=1. 621, P>0.05). It was suggested that GSTM1 null genotype might be a risk genotype of childhood ALL, while there as no correlation between GSTT1 null genotype and childhood ALL.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    There is increasing evidence from genome-wide association studies for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children, yet the effects of protein-coding variants on ALL risk have not been systematically evaluated. Here we show a missense variant...... of haematopoietic progenitor cells, and is preferentially retained in ALL tumour cells. Resequencing the CDKN2A-CDKN2B locus in 2,407 childhood ALL cases reveals 19 additional putative functional germline variants. These results provide direct functional evidence for the influence of inherited genetic variation...

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

    Directory of Open Access Journals (Sweden)

    Camila Silva Peres Cancela

    2013-08-01

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

  10. Acute lymphoblastic leukemia | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available of the trial TropicALL study; Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with L...oprofylaxe in kinderen behandeld voor Acute lymfatische leukemie met laag-moleculair-gewicht heparine: een g...dition or disease under investigation E.1.1Medical condition(s) being investigated Acute lymphoblastic leukemia Acute... Medical condition or disease under investigation E.1.2Version 17.1 E.1.2Level LLT E.1.2Classification code 10000845 E.1.2Term Acute

  11. Clinical and In Vitro Studies on Impact of High-Dose Etoposide Pharmacokinetics Prior Allogeneic Hematopoietic Stem Cell Transplantation for Childhood Acute Lymphoblastic Leukemia on the Risk of Post-Transplant Leukemia Relapse.

    Science.gov (United States)

    Sobiak, Joanna; Kazimierczak, Urszula; Kowalczyk, Dariusz W; Chrzanowska, Maria; Styczyński, Jan; Wysocki, Mariusz; Szpecht, Dawid; Wachowiak, Jacek

    2015-10-01

    The impact of etoposide (VP-16) plasma concentrations on the day of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on leukemia-free survival in children with acute lymphoblastic leukemia (ALL) was studied. In addition, the in vitro effects of VP-16 on the lymphocytes proliferation, cytotoxic activity and on Th1/Th2 cytokine responses were assessed. In 31 children undergoing allo-HSCT, VP-16 plasma concentrations were determined up to 120 h after the infusion using the HPLC-UV method. For mentioned in vitro studies, VP-16 plasma concentrations observed on allo-HSCT day were used. In 84 % of children, VP-16 plasma concentrations (0.1-1.5 μg/mL) were quantifiable 72 h after the end of the drug infusion, i.e. when allo-HSCT should be performed. In 20 (65 %) children allo-HSCT was performed 4 days after the end of the drug infusion, and VP-16 was still detectable (0.1-0.9 μg/mL) in plasma of 12 (39 %) of them. Post-transplant ALL relapse occurred in four children, in all of them VP-16 was detectable in plasma (0.1-0.8 μg/mL) on allo-HSCT day, while there was no relapse in children with undetectable VP-16. In in vitro studies, VP-16 demonstrated impact on the proliferation activity of stimulated lymphocytes depending on its concentration and exposition time. The presence of VP-16 in plasma on allo-HSCT day may demonstrate an adverse effect on graft-versus-leukemia (GvL) reaction and increase the risk of post-transplant ALL relapse. Therefore, if 72 h after VP-16 administration its plasma concentration is still above 0.1 μg/mL then the postponement of transplantation for next 24 h should be considered to protect GvL effector cells from transplant material.

  12. Plasma levels of leptin and soluble leptin receptor and polymorphisms of leptin gene -18G > A and leptin receptor genes K109R and Q223R, in survivors of childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Gozdzik Jolanta

    2011-06-01

    Full Text Available Abstract Background Approximately 20% of children and adolescents in Europe are overweight. Survivors of pediatric acute lymphoblastic leukemia (ALL are at increased risk of overweight and obesity. The purpose of this study was to assess leptin and leptin soluble receptor levels, as well as polymorphisms of selected genes in survivors of pediatric ALL, and the influence of chemo- and radiotherapy on development of overweight in the context of leptin regulation. Methods Eighty two patients (55% males, of median age 13.2 years (m: 4.8 years; M: 26.2 years were included in the study. The ALL therapy was conducted according to modified Berlin-Frankfurt-Munster (BFM; n = 69 regimen or New York (n = 13 regimen. In 38% of patients cranial radiotherapy (CRT was used in median dose of 18.2Gy (m: 14Gy; M: 24Gy. Median age at diagnosis was 4.5 (m: 1 year; M: 16.9 years and median time from completion of ALL treatment was 3.2 years (m: 0.5 year; M: 4.3 years. Patients with BMI ≥85 percentile were classified as overweight. Correlation of plasma levels of leptin and leptin soluble receptor, and polymorphisms of leptin gene -18G > A, leptin receptor genes K109R and Q223R, and the overweight status were analyzed in relation to gender, intensity of chemotherapy (high intensity vs. standard intensity regimens and to the use of CRT. Results Significant differences of leptin levels in patients treated with and without CRT, both in the entire study group (22.2+/- 3.13 ng/ml vs. 14.9+/-1.6 ng/ml; p Conclusions The prevalence of overweight in our cohort was higher than in general European population (31% vs 20% and increased regardless of the use of CRT. Leptin and leptin receptor levels may be used as useful markers of high risk of becoming overweight in ALL survivors, particularly in females treated with CRT. Polymorphisms of leptin gene -18G > A and leptin receptor genes K109R and Q223R were not associated with overweight status in ALL survivors.

  13. Acute myeloid leukaemia after treatment for acute lymphoblastic leukaemia in girl with Bloom syndrome.

    Science.gov (United States)

    Adams, Madeleine; Jenney, Meriel; Lazarou, Laz; White, Rhian; Birdsall, Sanda; Staab, Timo; Schindler, Detlev; Meyer, Stefan

    2013-09-18

    Bloom syndrome (BS) is an inherited genomic instability disorder caused by disruption of the BLM helicase and confers an extreme cancer predisposition. Here we report on a girl with BS who developed acute lymphoblastic leukaemia (ALL) at age nine, and treatment-related acute myeloid leukaemia (t-AML) aged 12. She was compound heterozygous for the novel BLM frameshift deletion c.1624delG and the previously described c.3415C>T nonsense mutation. Two haematological malignancies in a child with BS imply a fundamental role for BLM for normal haematopoiesis, in particular in the presence of genotoxic stress.

  14. Suppressed neutrophil function in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Tanaka, Fumiko; Goto, Hiroaki; Yokosuka, Tomoko; Yanagimachi, Masakatsu; Kajiwara, Ryosuke; Naruto, Takuya; Nishimaki, Shigeru; Yokota, Shumpei

    2009-10-01

    Infection is a major obstacle in cancer chemotherapy. Neutropenia has been considered to be the most important risk factor for severe infection; however, other factors, such as impaired neutrophil function, may be involved in susceptibility to infection in patients undergoing chemotherapy. In this study, we analyzed neutrophil function in children with acute lymphoblastic leukemia (ALL). Whole blood samples were obtained from 16 children with ALL at diagnosis, after induction chemotherapy, and after consolidation chemotherapy. Oxidative burst and phagocytic activity of neutrophils were analyzed by flow cytometry. Oxidative burst of neutrophils was impaired in ALL patients. The percentage of neutrophils with normal oxidative burst after PMA stimulation was 59.0 +/- 13.2 or 70.0 +/- 21.0% at diagnosis or after induction chemotherapy, respectively, which was significantly lower compared with 93.8 +/- 6.1% in healthy control subjects (P = 0.00004, or 0.002, respectively); however, this value was normal after consolidation chemotherapy. No significant differences were noted in phagocytic activity in children with ALL compared with healthy control subjects. Impaired oxidative burst of neutrophils may be one risk factor for infections in children with ALL, especially in the initial periods of treatment.

  15. The genomic landscape of hypodiploid acute lymphoblastic leukemia.

    Science.gov (United States)

    Holmfeldt, Linda; Wei, Lei; Diaz-Flores, Ernesto; Walsh, Michael; Zhang, Jinghui; Ding, Li; Payne-Turner, Debbie; Churchman, Michelle; Andersson, Anna; Chen, Shann-Ching; McCastlain, Kelly; Becksfort, Jared; Ma, Jing; Wu, Gang; Patel, Samir N; Heatley, Susan L; Phillips, Letha A; Song, Guangchun; Easton, John; Parker, Matthew; Chen, Xiang; Rusch, Michael; Boggs, Kristy; Vadodaria, Bhavin; Hedlund, Erin; Drenberg, Christina; Baker, Sharyn; Pei, Deqing; Cheng, Cheng; Huether, Robert; Lu, Charles; Fulton, Robert S; Fulton, Lucinda L; Tabib, Yashodhan; Dooling, David J; Ochoa, Kerri; Minden, Mark; Lewis, Ian D; To, L Bik; Marlton, Paula; Roberts, Andrew W; Raca, Gordana; Stock, Wendy; Neale, Geoffrey; Drexler, Hans G; Dickins, Ross A; Ellison, David W; Shurtleff, Sheila A; Pui, Ching-Hon; Ribeiro, Raul C; Devidas, Meenakshi; Carroll, Andrew J; Heerema, Nyla A; Wood, Brent; Borowitz, Michael J; Gastier-Foster, Julie M; Raimondi, Susana C; Mardis, Elaine R; Wilson, Richard K; Downing, James R; Hunger, Stephen P; Loh, Mignon L; Mullighan, Charles G

    2013-03-01

    The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32-39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.

  16. Transplant Outcomes for Children with Hypodiploid Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Mehta, Parinda A.; Zhang, Mei-Jie; Eapen, Mary; He, Wensheng; Seber, Adriana; Gibson, Brenda; Camitta, Bruce M.; Kitko, Carrie L.; Dvorak, Christopher C.; Nemecek, Eneida R.; Frangoul, Haydar A.; Abdel-Azim, Hisham; Kasow, Kimberly A.; Lehmann, Leslie; Vicent, Marta Gonzalez; Diaz Pérez, Miguel A.; Ayas, Mouhab; Qayed, Muna; Carpenter, Paul A.; Jodele, Sonata; Lund, Troy C.; Leung, Wing H.; Davies, Stella M.

    2015-01-01

    Children with hypodiploid acute lymphoblastic leukemia (ALL) have inferior outcomes despite intensive risk adapted chemotherapy regimens. We describe 78 children with hypodiploid ALL who underwent hematopoietic stem cell transplant (HSCT) between 1990 and 2010. Thirty nine (50%) patients had ≤ 43 chromosomes, 12 (15%) had 44 chromosomes and 27 (35%) had 45 chromosomes. Forty three (55%) patients were transplanted in first remission (CR1) while 35 (45%) were transplanted in ≥CR2. Twenty nine patients (37%) received a graft from a related donor and 49 (63%) from an unrelated donor. All patients received a myeloablative conditioning regimen. The 5-year probabilities of leukemia-free survival (LFS), overall survival (OS), relapse, and treatment related mortality (TRM) for the entire cohort were 51%, 56%, 27% and 22% respectively. Multivariate analysis confirmed that mortality risks were higher for patients transplanted in CR2 (HR 2.16, p=0.05), with chromosome number ≤43 (HR 2.15, p=0.05) and for those transplanted in the first decade of the study period (HR 2.60, p=0.01). Similarly, treatment failure risks were higher with chromosome number ≤43 (HR 2.28, p=0.04) and the earlier transplant period (HR 2.51, p=0.01). Although survival is better with advances in donor selection and supportive care, disease-related risk factors significantly influence transplantation outcomes. PMID:25865650

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

    Science.gov (United States)

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

    2011-08-01

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

  18. Acute Lymphoblastic Leukemia with Eosinophilia and Strongyloides Stercoralis Hyperinfection

    Directory of Open Access Journals (Sweden)

    Yadollah Zahedpasha

    2011-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Mehrdad Mirouliaei

    2013-01-01

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

  20. The mystery of electroencephalography in acute lymphoblastic leukemia.

    Science.gov (United States)

    Goldberg-Stern, Hadassa; Cohen, Rony; Pollak, Lea; Kivity, Sara; Eidlitz-Markus, Tal; Stark, Batya; Yaniv, Isaac; Shuper, Avinoam

    2011-04-01

    The aim of the study was to evaluate changes in electroencephalogram (EEG) recordings during the course of acute lymphoblastic leukemia (ALL) in children. The study group consisted of 48 children with ALL who underwent a total of 72 EEGs at various stages of the disease. The medical files were reviewed for pertinent clinical data, and the EEGs were evaluated for changes in brain activity. Abnormal background activity was noted in 52.2% of the EEGs done at 1-10 days of therapy, in 43.5% of those done at 10-60 days, and only 4.3% of those done at later stages (p=0.037). These findings, together with earlier reports, suggest that early-stage ALL, even before treatment, may be associated with excessive slow EEG activity, which improves over time. The EEG changes, by themselves, are not an indication of central nervous system leukemia or a predictor of later seizures or other central nervous system involvement.

  1. Invasive Pulmonary Aspergillosis in a Patient with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Orhan Ayyıldız

    2004-01-01

    Full Text Available Fungal infections are common and life-threatening among immunosupressive patients.Invasive pulmonar aspergilloz (IPA generally occurs when Aspergillus inhaled, but rarelywith the hematogen spread of dermal or gastrointestinal Aspergillus. We present here, IPA ina 58 year-old male patient with acute lymphoblastic leukemia (ALL. He was admitted to ourclinic with fatigue, weakness, pansitopenia, and with petechia. Supportive treatment,vincristine and prednisone was initiated. Chest roentgenogram was normal. Dyspnea andfever (39.5’C were seen after 1 month of therapy. Thorax high resolution computerizedtomography was obtained and cavitary lesion was seen in the left upper-anterior segment oflung. Sputum and blood culture were negative. In spite of the empiric use of Meropenem 3gr/d, Vancomycin 2 gr/d and fluconazole 200 mg/d, fever was not turned to normal andclinical symptoms were not healed. On the fifth days of therapy amphotericin-B was initiatedand the other antibiotics were stopped after 3 days. General symptoms were healed on the 8thdays. Radiologic findings were improved partially after 20 days. The patient clinically is welland remains in remission and radiologic findings were turn to near normal after 10 monthsof treatment. We aimed to emphasis about treatment of empirical Amphotericin-B incritically ill patient with ALL.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  4. Recent advances in the management of pediatric acute lymphoblastic leukemia [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Jan Starý

    2016-11-01

    Full Text Available Acute lymphoblastic leukemia (ALL is the most common malignancy in childhood. Despite enormous improvement of prognosis during the last half century, ALL remains a major cause of childhood cancer-related mortality. During the past decade, whole genomic methods have enhanced our knowledge of disease biology. Stratification of therapy according to early treatment response measured by minimal residual disease allows risk group assignment into different treatment arms, ranging from reduction to intensification of treatment. Progress has been achieved in academic clinical trials by optimization of combined chemotherapy, which continues to be the mainstay of contemporary treatment. The availability of suitable volunteer main histocompatibility antigen-matched unrelated donors has increased the rates of hematopoietic stem cell transplantation (HSCT over the past two decades. Allogeneic HSCT has become an alternative treatment for selected, very-high-risk patients. However, intensive treatment burdens children with severe acute toxic effects that can cause permanent organ damage and even toxic death. Immunotherapeutic approaches have recently come to the forefront in ALL therapy. Monoclonal antibodies blinatumomab and inotuzumab ozogamicin as well as gene-modified T cells directed to specific target antigens have shown efficacy against resistant/relapsed leukemia in phase I/II studies. Integration of these newer modalities into combined regimens with chemotherapy may rescue a subset of children not curable by contemporary therapy. Another major challenge will be to incorporate less toxic regimens into the therapy of patients with low-risk disease who have a nearly 100% chance of being cured, and the ultimate goal is to improve their quality of life while maintaining a high cure rate.

  5. Unilateral Exudative Retinal Detachment as the Sole Presentation of Relapsing Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Fatih Mehmet Azık

    2012-06-01

    Full Text Available Ocular findings are rarely the initial symptom of leukemia, although up to 90% of all leukemia patients have fundus changes during the course of the disease. Herein we report a relapsing acute lymphoblastic leukemia patient with the sole presentation of sudden visual loss and exudative retinal detachment. An 8-year-old boy with acute lymphoblastic leukemia developed sudden visual loss during his first remission period. Bullous retinal detachment with total afferent pupillary defect was observed. Orbital magnetic resonance imaging revealed an intraocular mass lesion; simultaneously obtained bone marrow and cerebrospinal fluid samples showed no evidence of leukemic cells. Following local irradiation, and systemic and intrathecal chemotherapy the mass disappeared. Local irradiation, and systemic and intrathecal chemotherapy effectively controlled the isolated ocular relapse of acute lymphoblastic leukemia and eliminated the need for enucleation.

  6. Acute leukemia in early childhood

    Directory of Open Access Journals (Sweden)

    M. Emerenciano

    2007-06-01

    Full Text Available Acute leukemia in early childhood is biologically and clinically distinct. The particular characteristics of this malignancy diagnosed during the first months of life have provided remarkable insights into the etiology of the disease. The pro-B, CD10 negative immunophenotype is typically found in infant acute leukemia, and the most common genetic alterations are the rearrangements of the MLL gene. In addition, the TEL/AML1 fusion gene is most frequently found in children older than 24 months. A molecular study on a Brazilian cohort (age range 0-23 months has detected TEL/AML1+ve (N = 9, E2A/PBX1+ve (N = 4, PML/RARA+ve (N = 4, and AML1/ETO+ve (N = 2 cases. Undoubtedly, the great majority of genetic events occurring in these patients arise prenatally. The environmental exposure to damaging agents that give rise to genetic changes prenatally may be accurately determined in infants since the window of exposure is limited and known. Several studies have shown maternal exposures that may give rise to leukemogenic changes. The Brazilian Collaborative Study Group of Infant Acute Leukemia has found that mothers exposed to dipyrone, pesticides and hormones had an increased chance to give birth to babies with infant acute leukemia [OR = 1.48 (95%CI = 1.05-2.07, OR = 2.27 (95%CI = 1.56-3.31 and OR = 9.08 (95%CI = 2.95-27.96], respectively. This review aims to summarize recent clues that have facilitated the elucidation of the biology of early childhood leukemias, with emphasis on infant acute leukemia in the Brazilian population.

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

    Science.gov (United States)

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

    2016-01-01

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

  8. Temporal lobe epilepsy with hippocampal sclerosis in acute lymphoblastic leukemia.

    Science.gov (United States)

    Kasai-Yoshida, Emi; Ogihara, Masaaki; Ozawa, Miwa; Nozaki, Taiki; Morino, Michiharu; Manabe, Atsushi; Hosoya, Ryota

    2013-07-01

    Of 71 acute lymphoblastic leukemia survivors at our hospital over the past 10 years, 2 children developed mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). This is the first report to describe the clinical course of MTLE-HS observed longitudinally by EEG and MRI. Patient 1 experienced a seizure during chemotherapy involving intrathecal methotrexate. Postseizure MRI suggested methotrexate encephalopathy or leukemic invasion. Anticonvulsant therapy was initiated; subsequent EEGs and MRIs revealed normal results. Three years after chemotherapy, a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. Five years after chemotherapy, the patient developed MTLE-HS comprising complex partial seizures, typical temporal spikes on EEG, and hippocampal sclerosis (HS). Patient 2 did not experience seizures during chemotherapy. Four years later, the patient started experiencing complex partial seizures, and a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. A clinical picture of MTLE-HS developed 2 years later. In both patients, nonspecific EEG abnormalities (ie, diffuse, irregular spike-and-wave activity) preceded the appearance of HS on MRI by 2 years, suggesting an insidious advance of HS during the latent period. Such atypical EEG findings may indicate MTLE-HS during follow-up of leukemia patients. MTLE-HS develops several years after an initial precipitating incident such as prolonged seizures, central nervous system infection, and brain trauma. In our cases, the initial precipitating incident may have been chemotherapy and/or prolonged seizures. Thus, MTLE-HS associated with leukemia may not be as rare as generally believed. A large cohort study of late neurologic complications is warranted.

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

    Directory of Open Access Journals (Sweden)

    Ramyar Asghar

    2009-06-01

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

  10. Improved Prognosis for Older Adolescents With Acute Lymphoblastic Leukemia

    Science.gov (United States)

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

    2011-01-01

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

  11. [Alcaligenes xylosoxidans bacteremia in a patient with acute lymphoblastic leukemia].

    Science.gov (United States)

    Aydemir, Zeynep Alp; Ozdemir, Nihal; Celik, Nigar; Celkan, Tiraje

    2009-07-01

    Alcaligenes xylosoxidans which is an aerobic, non-fermentative gram-negative bacillus found in aqueous environments and human flora, can lead to opportunistic infections. It causes infections in elderly, immunocompromised patients, patients with chronic disorders or premature infants. In this report, a case of A. xylosoxidans bacteremia that developed in a child with acute lymphoblastic leukemia (ALL) was presented. Four-years-old male patient under ALL induction therapy was admitted with symptoms of lethargy, headache, somnolence, and fever (39 degrees C). Cerebrospinal fluid, blood, throat and urine cultures were taken from the patient and empirical treatment with sulbactam cefoperazon and amikacin was initiated. Blood cultures in BacT Alert 3D (Bio Merieux, France) revealed the growth of a gram-negative coccobacillus. The agent which was non-fermentative, indol and H2S negative, was identified as A. xylosoxidans by API 20 NE (Bio Merieux, France). Since fever continued under the current antibiotic treatment, the therapy was switched to imipenem (90 mg/kg 3x/day) and the patient's condition improved markedly after 24 hours. Disc diffusion susceptibility testing of the isolate revealed that it was resistant to ampicillin, cephalothin, cefuroxime, cefoxitin, cefotaxime, amikacin, netilmicin and gentamicin; susceptible to amoxicillin clavulanate, piperacillin tazobactam, seftazidime, cefepime, imipenem and ciprofloxacin. Following 14 days of imipenem therapy, the patient recovered and discharged from the hospital on routine follow-up. It is important to consider A. xylosoxidans as a possible causative agent particularly in the infections that develop in high risk patients at oncology, dialysis and neonatal intensive care units.

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

    LENUS (Irish Health Repository)

    Kelly, Kevin

    2008-12-01

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

  13. UNUSUAL CLINICAL PRESENTATION OF RELAPSE IN PATIENT WITH ACUTE LYMPHOBLASTIC LEUKEMIA.

    Directory of Open Access Journals (Sweden)

    Vanya Slavcheva

    2015-04-01

    Full Text Available Acute lymphoblastic leukemia is a disease, which is more common in children. We report a clinical case of a patient aged 25. Thirty-two months before his last admission in Hematology clinic, acute pre- B lymphoblastic leukemia had been diagnosed and treated till March 2012. In September 2013 after bone marrow aspiration, flow cytometric analysis, trepan biopsy and biopsy of the kidney had been carried out, the patient was diagnosed with first late relapse, involving bone marrow and kidney. A second remission was achieved using Berlin- Frankfurt– Munster chemotherapy [BFM] and allogenic stem cell transplantation was performed.

  14. [Acute benign ataxia in childhood].

    Science.gov (United States)

    Grippo, J; Arroyo, H A; Rocco, R D; Iraola, J

    1979-01-01

    The patogenesis and etiology of acute ataxia in childhood is not well known. It may occur without previous symptoms or may be the expression of specific infectious diseases. Forty patients hospitalized at the Hospital de Niños de Buenos Aires en 1972-1978, were studied. The neurological manifestations showed an acute onset, being ataxia the main sign, associate to tremor, nystagmus, dysartria, oculo-motor paresia, muscular weakness, and hyporeflexia. Most of the patients (82%) became cured within the first four weeks. It is advisable to establish a follow-up with periodic controls, mainly in those patients in whom an association with previous infectious diseases did not exist to be able to detect an association with degenerative or desmyelinizing diseases.

  15. mRNA overexpression of BAALC: A novel prognostic factor for pediatric acute lymphoblastic leukemia

    OpenAIRE

    Azizi, Zahra; Rahgozar, Soheila; Moafi, Alireza; DABAGHI, MOHAMMAD; NADIMI, MOTAHAREH

    2015-01-01

    BAALC is a novel molecular marker in leukemia that is highly expressed in patients with acute leukemia. Increased expression levels of BAALC are known as poor prognostic factors in adult acute myeloid and lymphoid leukemia. The purpose of the present study was to evaluate the prognostic significance of the BAALC gene expression levels in pediatric acute lymphoblastic leukemia (ALL) and its association with MDR1. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the...

  16. CD123在儿童急性B淋巴细胞白血病中的表达及其在微小残留病检测中的应用%Expressions of CD123 in childhood B-lineage acute lymphoblastic leukemia and the application of CD123 in minimal residual disease detection

    Institute of Scientific and Technical Information of China (English)

    计雪强; 季正华; 邵惠江; 王红英; 何亚香; 朱宏; 邵雪君

    2012-01-01

    Objective: Detecting the expression of CD123 in childhood B-lineage acute lymphoblastic leukemia ( B-ALL ) and discussing the application and significance of CD123 in minimal residual disease ( MRD ) detection. Methods: With the normal children bone marrow lymphocytes as control, multiparame-ter flow cytometry was used to study the bone marrow lymphocytes immunophenotype and the expression of CD123 in 91 cases of children with B-ALL, 78 cases of which were underwent bone marrow cells chromosome cultivation and cytogenetic analysis. 65 cases of B-ALL children with CD123 positive expression were screened and monitored by CD10/CD123/CD34/CD19 in MRD detection. Results: The expression of CD 123 in normal children bone marrow lymphocytes was negative, while 65 cases of 91 in B-ALL children was positive( positive rate 71.43% ), and the expression level of CD123 was negatively correlated with the leukemic cells maturity. When children had a high expression of CD34, the expression of CD123 was also in a high level. The results of cytogenetic analysis showed that hyperdiploid B-ALL children had a higher level of CD123 expression, when comparing with the non-hyperdiploid cases. Forty-seven cases of B-ALL children ( 51. 65% ) had a high level of CD 123 expression, and CD 123 could be used as an effective marker for MRD monitoring. Conclusion: Most of B-ALL children had an expression of CD123 , which was negatively correlated with the leukemic cells maturity. CD123 can be used as a maker for MRD monitoring in childhood B-ALL.%目的:检测细胞表面抗原CD123在儿童急性B淋巴细胞白血病(B-lineage acute lymphoblastic leukemia,B-ALL)中的表达,并探讨其在儿童B-ALL微小残留病(minimal residual disease,MRD)检测中的应用及意义.方法:以健康儿童骨髓淋巴细胞为对照,应用多参数流式细胞术检测91例儿童B-ALL患者骨髓淋巴细胞免疫表型及CD123的表达,其中78例B-ALL患者进行了骨髓细胞染色体培养及

  17. Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies.

    Science.gov (United States)

    van Dongen, Jacques J M; van der Velden, Vincent H J; Brüggemann, Monika; Orfao, Alberto

    2015-06-25

    Monitoring of minimal residual disease (MRD) has become routine clinical practice in frontline treatment of virtually all childhood acute lymphoblastic leukemia (ALL) and in many adult ALL patients. MRD diagnostics has proven to be the strongest prognostic factor, allowing for risk group assignment into different treatment arms, ranging from significant treatment reduction to mild or strong intensification. Also in relapsed ALL patients and patients undergoing stem cell transplantation, MRD diagnostics is guiding treatment decisions. This is also why the efficacy of innovative drugs, such as antibodies and small molecules, are currently being evaluated with MRD diagnostics within clinical trials. In fact, MRD measurements might well be used as a surrogate end point, thereby significantly shortening the follow-up. The MRD techniques need to be sensitive (≤10(-4)), broadly applicable, accurate, reliable, fast, and affordable. Thus far, flow cytometry and polymerase chain reaction (PCR) analysis of rearranged immunoglobulin and T-cell receptor genes (allele-specific oligonucleotide [ASO]-PCR) are claimed to meet these criteria, but classical flow cytometry does not reach a solid 10(-4), whereas classical ASO-PCR is time-consuming and labor intensive. Therefore, 2 high-throughput technologies are being explored, ie, high-throughput sequencing and next-generation (multidimensional) flow cytometry, both evaluating millions of sequences or cells, respectively. Each of them has specific advantages and disadvantages.

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

    Science.gov (United States)

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

    2004-05-01

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

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Lazić Jelena

    2009-01-01

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

  1. L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase

    Science.gov (United States)

    Pieters, Rob; Hunger, Stephen P; Boos, Joachim; Rizzari, Carmelo; Silverman, Lewis; Baruchel, Andre; Goekbuget, Nicola; Schrappe, Martin; Pui, Ching-Hon

    2010-01-01

    Asparaginases are a cornerstone of treatment protocols for acute lymphoblastic leukemia (ALL) and are used for remission induction and intensification treatment in all pediatric regimens and in the majority of adult protocols. Extensive clinical data have shown that intensive asparaginase treatment improves clinical outcomes in childhood ALL. Three asparaginase preparations are available; the native asparaginase derived from Escherichia coli (E. coli-asparaginase), a pegylated form of this enzyme (PEG-asparaginase) and a product isolated from Erwinia chrysanthemi, i.e. Erwinia asparaginase. Clinical hypersensitivity reactions and silent inactivation due to antibodies against E.coli-asparaginase, lead to inactivation of E-Coli asparaginase in up to 60% of cases. Current treatment protocols include E. coli-asparaginase or PEG-asparaginase for first-line treatment of ALL. Typically, patients exhibiting sensitivity to one formulation of asparaginase are switched to another product to ensure they receive the most efficacious treatment regimen possible. Erwinia asparaginase is used as a second- or third-line treatment in European and US protocols. Despite the universal inclusion of asparaginase in such treatment protocols, there is much debate regarding the optimal formulation and dosage of these agents. This manuscript provides an overview of available evidence to make recommendations for optimal use of Erwinia asparaginase in the treatment of ALL. PMID:20824725

  2. TET2 promoter DNA methylation and expression analysis in pediatric B-cell acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Ewa Musialik

    2014-03-01

    Full Text Available TET2 is a novel tumor suppressor gene involved in several hematological malignancies of myeloid and lymphoid origin. Besides loss-of-function mutations and deletions, hypermethylation of the CpG island at the TET2 promoter was found in human cancer. Previous analysis revealed no TET2 mutations in acute lymphoblastic leukemia (ALL. Since the TET2 promoter methylation status in pediatric ALL has not been reported, the aim of the present study was to determine if promoter hypermethylation may be a mechanism of TET2 inactivation in a group of pediatric ALL cases. Methylation of TET2 promoter region in one (1/45 ALL B-common patient was detected by methylation specific polymerase chain reaction (PCR and subsequently analyzed by bisulfite sequencing. We found no correlation between promoter methylation and gene expression, measured by quantitative reverse transcriptase-PCR, however the level of TET2 expression in ALL group was significantly decreased compared to children’s normal peripheral blood mononuclear cells and isolated B-cells. TET2 promoter hypermethylation seems to have limited clinical relevance in childhood B-cell ALL due to its low frequency.

  3. ETV6-RUNX1 Rearrangement in Tunisian Pediatric B-Lineage Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Abir Gmidène

    2009-01-01

    Full Text Available In this study, Forty-one out of fifty-seven Tunisian children with B-lineage acute lymphoblastic leukemia (B-ALL, and without cytogenetically detectable recurrent abnormalities at the time of the diagnosis, were evaluated by fluorescence in situ hybridization (FISH for the t(12;21. This translocation leads ETV6-RUNX1 (previously TEL-AML1 fusion gene. 16 patients (28% had ETV6-RUNX1 rearrangement. In addition to this rearrangement, two cases showed a loss of the normal ETV6 allele, and three others showed an extra signal of the RUNX1 gene. Seven patients without ETV6-RUNX1 rearrangement showed extra signals of the RUNX1 gene. One out of the 7 patients was also associated with a t(3;12 identified by FISH. This is the first Tunisian study in which we report the incidence of t(12;21 among childhood B-lineage ALL and in which we have found multiple copies of RUNX1. Finally, our findings confirm that additional or secondary genetic changes are commonly encountered in pediatric B-lineage ALL with ETV6-RUNX1 gene fusion which is envisaged to play a pivotal role in disease progression.

  4. Constitutional abnormalities of chromosome 21 predispose to iAMP21-acute lymphoblastic leukaemia.

    Science.gov (United States)

    Harrison, Christine J; Schwab, Claire

    2016-03-01

    In addition to Down syndrome, individuals with other constitutional abnormalities of chromosome 21 have an increased risk of developing childhood acute lymphoblastic leukaemia (ALL). Specifically, carriers of the Robertsonian translocation between chromosomes 15 and 21, rob(15;21) (q10; q10)c, have ∼2,700 increased risk of developing ALL with iAMP21 (intrachromosomal amplification of chromosome 21). In these patients, chromosome 15 as well as chromosome 21 is involved in the formation of iAMP21, referred to here as der(21)(15;21). Individuals with constitutional ring chromosomes involving chromosome 21, r(21)c, are also predisposed to iAMP21-ALL, involving the same series of mutational processes as seen in sporadic- and der(21)(15;21)-iAMP21 ALL. Evidence is accumulating that the dicentric nature of the Robertsonian and ring chromosome is the initiating factor in the formation of the complex iAMP21 structure. Unravelling these intriguing predispositions to iAMP21-ALL may provide insight into how other complex rearrangements arise in cancer.

  5. Prognostic value of cytogenetics in adult patients with Philadelphia-negative acute lymphoblastic leukemia.

    Science.gov (United States)

    Gómez-Seguí, Inés; Cervera, Jose; Such, Esperanza; Martínez-Cuadrón, David; Luna, Irene; Ibáñez, Mariam; López-Pavía, María; Gascón, Adriana; Roig, Mónica; Martínez, Jesús; Sanz, Jaime; Montesinos, Pau; Martín-Aragonés, Guillermo; Lorenzo, Ignacio; Senent, Leonor; Barragán, Eva; Cordón, Lourdes; Sempere, Amparo; Sanz, Guillermo F; Sanz, Miguel Angel

    2012-01-01

    The prognostic value of cytogenetics in adult acute lymphoblastic leukemia (ALL) is not as established as in childhood ALL. We have analyzed the outcome and prognostic value of karyotype in 84 adults diagnosed with Philadelphia-negative ALL from a single institution that received induction chemotherapy and had successful karyotype performed. The most frequent finding was normal karyotype in 35 (42%) cases, followed by aneuploidies in 20 cases (24%) and t(4;11)(q21;q23)/MLL/AF4 in 5 (6%), and the remaining 24(27%) cases carried miscellaneous clonal abnormalities. The group of patients with t(4;11)(q21;q23)/MLL/AF4, hypodiploidy and low hyperdiploidy (less than 50 chromosomes) showed a worse outcome than those with normal karyotype and miscellaneous abnormalities in terms of overall survival (OS) (3 years OS; 47% vs. 13%, p = 0.014) and relapse-free survival (RFS) (3 years RFS; 44% vs. 27%, p = 0.005). Other cytogenetic prognostic classifications reported to date were tested in our series, but any was fully reproducible. In conclusion, karyotype is a useful tool for risk assessment in adult ALL. We have confirmed the bad prognosis of t(4;11)(q21;q23)/MLL/AF4 and hypodiploidy. Besides, low hyperdiploidy could also define a high-risk group of patients who might be candidates for more intensive treatment.

  6. Bone Density in Pediatric Patients with Acute Lymphoblastic Leukemia (ALL: A Literature Review

    Directory of Open Access Journals (Sweden)

    Ali Ghassemi

    2015-02-01

    Full Text Available Introduction:  Acute Lymphoblastic Leukemia (ALL is the most common malignancy in children and the main form of childhood leukemia (75%. ALL different treatment options have a great impact on children weight and appetite. The improving prognosis for children with cancer refocuses attention to long-term outcomes with an emphasis on quality of life. More survival rate allows researchers to evaluate long term complication of ALL and its different treatment options such as endocrine abnormalities for example decreased bone mineral density. METHODS:  a systematic web base search was conducted in MEDLINE up to December 2014. We included articles with available abstract in English language, and participants younger than 18 years. Manual searching was done within the reference list of articles.  Two reviewers independently reviewed and assessed eligibility criteria, assessed quality, and extracted data. RESULTS:  Trace elements concentration decline due to malabsorption or inadequate intake in children with ALL. Osteopenia occurs more frequent in younger children and those who treated with higher doses of corticosteroids. CONCLUSION:  The dietary history of ALL patients who are at more risk for fractures and osteopenia should be screened by paying more attention to calcium and vitamin D intake.

  7. L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase.

    Science.gov (United States)

    Pieters, Rob; Hunger, Stephen P; Boos, Joachim; Rizzari, Carmelo; Silverman, Lewis; Baruchel, Andre; Goekbuget, Nicola; Schrappe, Martin; Pui, Ching-Hon

    2011-01-15

    Asparaginases are a cornerstone of treatment protocols for acute lymphoblastic leukemia (ALL) and are used for remission induction and intensification treatment in all pediatric regimens and in the majority of adult treatment protocols. Extensive clinical data have shown that intensive asparaginase treatment improves clinical outcomes in childhood ALL. Three asparaginase preparations are available: the native asparaginase derived from Escherichia coli (E. coli asparaginase), a pegylated form of this enzyme (PEG-asparaginase), and a product isolated from Erwinia chrysanthemi, ie, Erwinia asparaginase. Clinical hypersensitivity reactions and silent inactivation due to antibodies against E. coli asparaginase, lead to inactivation of E. coli asparaginase in up to 60% of cases. Current treatment protocols include E. coli asparaginase or PEG-asparaginase for first-line treatment of ALL. Typically, patients exhibiting sensitivity to one formulation of asparaginase are switched to another to ensure they receive the most efficacious treatment regimen possible. Erwinia asparaginase is used as a second- or third-line treatment in European and US protocols. Despite the universal inclusion of asparaginase in such treatment protocols, debate on the optimal formulation and dosage of these agents continues. This article provides an overview of available evidence for optimal use of Erwinia asparaginase in the treatment of ALL.

  8. Global characteristics of childhood acute promyelocytic leukemia.

    Science.gov (United States)

    Zhang, L; Samad, A; Pombo-de-Oliveira, M S; Scelo, G; Smith, M T; Feusner, J; Wiemels, J L; Metayer, C

    2015-03-01

    Acute promyelocytic leukemia (APL) comprises approximately 5-10% of childhood acute myeloid leukemia (AML) cases in the US. While variation in this percentage among other populations was noted previously, global patterns of childhood APL have not been thoroughly characterized. In this comprehensive review of childhood APL, we examined its geographic pattern and the potential contribution of environmental factors to observed variation. In 142 studies (spanning >60 countries) identified, variation was apparent-de novo APL represented from 2% (Switzerland) to >50% (Nicaragua) of childhood AML in different geographic regions. Because a limited number of previous studies addressed specific environmental exposures that potentially underlie childhood APL development, we gathered 28 childhood cases of therapy-related APL, which exemplified associations between prior exposures to chemotherapeutic drugs/radiation and APL diagnosis. Future population-based studies examining childhood APL patterns and the potential association with specific environmental exposures and other risk factors are needed.

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

    Directory of Open Access Journals (Sweden)

    Mintz Michelle

    2004-09-01

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

  10. Precursor B-cell acute lymphoblastic leukemia presenting as obstructive jaundice: a case report

    Directory of Open Access Journals (Sweden)

    Awasum Michael

    2011-07-01

    Full Text Available Abstract Introduction Acute leukemias very rarely present with jaundice. Herein we report a case of precursor B-cell acute lymphoblastic leukemia that presented with jaundice in an adult. Case presentation A 44-year-old Hispanic man presented with right upper quadrant abdominal pain and jaundice. His initial blood work revealed pancytopenia and hyperbilirubinemia. Direct bilirubin was more than 50% of the total. His imaging studies were unremarkable except for hepatomegaly. All blood screening tests for various hepatocellular etiologies were normal. A diagnosis of precursor B-cell acute lymphoblastic leukemia was made upon liver biopsy. It also showed lymphocytic infiltration of the hepatic parenchyma leading to bile stasis. The diagnosis was subsequently confirmed upon bone marrow biopsy. The patient was treated with a hyperfractionated cyclophosphamide/vincristine/doxorubicin/dexamethasone regimen. Conclusion Acute lymphoblastic leukemia should be one of the differential diagnoses that should be considered when initial work-up for jaundice is inconclusive. Some cases of acute lymphoblastic leukemia have been reported in both adults and children to have presented with the initial manifestation of jaundice, but only a few had no radiographic evidence of biliary obstruction. Such presentation can pose a serious diagnostic dilemma for clinicians. This manuscript attempts to highlight it. Moreover, we believe that if acute lymphoblastic leukemia presentations similar to this case continue to be reported in adults or children, a specific immunophenotypic expression and cytogenetic abnormality may be found to be associated with hepatic infiltration by leukemia. This may substantially contribute to the further understanding of the pathophysiology of this hematologic disease.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    The available guidelines for varicella vaccination of susceptible children with acute lymphoblastic leukemia (ALL) have become increasingly conservative. However, vaccination of those who have remained in continuous complete remission for 1 year and are receiving chemotherapy is still considered...... a reasonable option. There is little available data to allow a comparison of the risk versus benefit of vaccinating these patients....

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

    Directory of Open Access Journals (Sweden)

    Shah Kirit

    2004-07-01

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    NARCIS (Netherlands)

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

    2002-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    刘立民

    2013-01-01

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  20. A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Shah, S.; Schrader, K.A.; Waanders, E.; Timms, A.E.; Vijai, J.; Miething, C.; Wechsler, J.; Yang, J.; Hayes, J.; Klein, R.J.; Zhang, Jinghui; Wei, L.; Wu, G.; Rusch, M.; Nagahawatte, P.; Ma, J; Chen, S.C.; Song, G.; Cheng, J.; Meyers, P.; Bhojwani, D.; Jhanwar, S.; Maslak, P.; Fleisher, M.; Littman, J.; Offit, L.; Rau-Murthy, R.; Fleischut, M.H.; Corines, M.; Murali, R.; Gao, X.; Manschreck, C.; Kitzing, T.; Murty, V.V.; Raimondi, S.C.; Kuiper, R.P.; Simons, A.; Schiffman, J.D.; Onel, K.; Plon, S.E.; Wheeler, D.A.; Ritter, D.; Ziegler, D.S.; Tucker, K.; Sutton, R.; Chenevix-Trench, G.; Li, J.; Huntsman, D.G.; Hansford, S.; Senz, J.; Walsh, T.; Lee, M. van der; Hahn, C.N.; Roberts, K.G.; King, M.C.; Lo, S.M.; Levine, R.L.; Viale, A.; Socci, N.D.; Nathanson, K.L.; Scott, H.S.; Daly, M.; Lipkin, S.M.; Lowe, S.W.; Downing, J.R.; Altshuler, D.; Sandlund, J.T.; Horwitz, M.S.; Mullighan, C.G.; Offit, K.

    2013-01-01

    Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL), but inherited mutations of PAX5 have not previously been described. Here we report a new heterozygous germline variant, c.547G>A (p.Gly1

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  2. Analysis of handwriting of children during treatment for acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Reinders-Messelink, H.A.; Schoemaker, M.M.; Göeken, L.N.H.; Bökkerink, J.P.M.; Kamps, W.A.

    2001-01-01

    Background. Children treated for acute lymphoblastic leukemia (ALL) often complain about handwriting problems. Procedure. Using a computerized writing task, we have prospectively studied the processes necessary for the production of handwriting movements in I I children (5-12 years old) during treat

  3. Fatal Aspergillus rhinosinusitis during induction chemotherapy in a child with acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Vlaardingerbroek, H.; Flier, M. van der; Borgstein, J.A.; Lequin, M.H.; Sluis, I.M. van der

    2009-01-01

    Invasive fungal infections are a major problem in patients treated for hematologic malignancies. We report a 3-year-old girl who suffered from febrile neutropenia during induction therapy for acute lymphoblastic leukemia. Initial chest computed tomography revealed no evidence of intrapulmonary funga

  4. Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in pregnancy.

    Science.gov (United States)

    Mainor, Candace B; Duffy, Alison P; Atkins, Kristin L; Kimball, Amy S; Baer, Maria R

    2016-04-01

    BCR-ABL inhibitors administered in conjunction with chemotherapy have significantly improved outcomes in Philadelphia chromosome-positive acute lymphoblastic leukemia but, for patients diagnosed during pregnancy, data on risks to the fetus are limited. We report a woman treated with chemotherapy and imatinib mesylate who delivered a healthy baby at 30 weeks, and we discuss available data.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  6. Acute kidney injury and bilateral symmetrical enlargement of the kidneys as first presentation of B-cell lymphoblastic lymphoma.

    Science.gov (United States)

    Shi, Su-fang; Zhou, Fu-de; Zou, Wan-zhong; Wang, Hai-yan

    2012-12-01

    Lymphoblastic lymphoma is an uncommon subtype of lymphoid neoplasm in adults. Acute kidney injury at initial presentation due to lymphoblastic lymphoma infiltration of the kidneys has rarely been described. We report a 19-year-old woman who presented with acute kidney injury due to massive lymphomatous infiltration of the kidneys. The diagnosis of B-cell lymphoblastic lymphoma was established by immunohistochemical study of the biopsied kidney. The patient had an excellent response to the VDCLP protocol (vincristine, daunomycin, cyclophosphamide, asparaginase, and dexamethasone) with sustained remission. We recommend that lymphomatous infiltration be considered in patients presenting with unexplained acute kidney injury and enlarged kidneys.

  7. Mosaic Down syndrome and acute lymphoblastic B cell-leukemia. Case report

    Directory of Open Access Journals (Sweden)

    Parra-Baltazar, Isabel Mónica

    2016-10-01

    Full Text Available Down syndrome (DS or trisomy 21 is a constitutional chromosomal abnormality, which may be mosaic in 1 % to 4 % of cases. DS mosaic diagnosis is difficult because most patients have a normal phenotype and show no significant clinical abnormalities. Patients with DS have a higher risk of developing acute leukemia such as acute lymphoblastic leukemia (ALL. We report the case of a 19-year old woman with mosaic trisomy 21 and ALL.

  8. High sensitivity of flow cytometry improves detection of occult leptomeningeal disease in acute lymphoblastic leukemia and lymphoblastic lymphoma.

    Science.gov (United States)

    Del Principe, Maria Ilaria; Buccisano, Francesco; Cefalo, Mariagiovanna; Maurillo, Luca; Di Caprio, Luigi; Di Piazza, Fabio; Sarlo, Chiara; De Angelis, Gottardo; Irno Consalvo, Maria; Fraboni, Daniela; De Santis, Giovanna; Ditto, Concetta; Postorino, Massimiliano; Sconocchia, Giuseppe; Del Poeta, Giovanni; Amadori, Sergio; Venditti, Adriano

    2014-09-01

    Conventional cytology (CC) of cerebrospinal fluid (CSF) fails to demonstrate malignant cells in up to 45 % of patients with acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LL) in whom occult leptomeningeal disease is present. Flow cytometry (FCM) is considered more sensitive than CC, but clinical implications of CC negativity/CC positivity are not yet established. CSF samples from 38 adult patients with newly diagnosed ALL/LL were examined. Five (13 %) and nine (24 %) specimens were CC positive-FC positive (FCM(pos)/CC(pos)) and CC negative-FC positive (CC(neg)/FCM(pos)), respectively. The remaining 24 (63 %) samples were double negative (CC(neg)/FCM(neg)) (p = 0.001). CC(neg)/FCM(pos) patients showed a significantly shorter overall survival (OS) compared to CC(neg)/FCM(neg) ones. In multivariate analysis, the status of single FCM positivity was demonstrated to affect independently duration of OS (p = 0.005). In conclusion, FCM significantly improves detection of leptomeningeal occult localization in ALL/LL and appears to anticipate an adverse outcome. Further prospective studies on larger series are needed to confirm this preliminary observation.

  9. Individualized toxicity-titrated 6-mercaptopurine increments during high-dose methotrexate consolidation treatment of lower risk childhood acute lymphoblastic leukaemia. A Nordic Society of Paediatric Haematology and Oncology (NOPHO) pilot study

    DEFF Research Database (Denmark)

    Frandsen, Thomas L; Abrahamsson, Jonas; Lausen, Birgitte;

    2011-01-01

    This study explored the feasibility and toxicity of individualized toxicity-titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment with High-dose methotrexate (HDM) (5000 mg/m(2), ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m(2...... the remaining patients (P = 0·03). This study shows individualized toxicity-titrated 6MP dosing during consolidation is feasible without increased risk of toxicity....

  10. Prospective study on incidence, risk factors, and long-term outcome of osteonecrosis in pediatric acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Winkel, M.L. te; Pieters, R.; Hop, W.C.J.; Groot-Kruseman, H.A. de; Lequin, M.H.; Sluis, I.M. van der; Bokkerink, J.P.M.; Leeuw, J.A. de; Bruin, M.C.; Egeler, R.M.; Veerman, A.J.P.; Heuvel-Eibrink, M.M. van den

    2011-01-01

    PURPOSE: We studied cumulative incidence, risk factors, therapeutic strategies, and outcome of symptomatic osteonecrosis in pediatric patients with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Cumulative incidence of osteonecrosis was assessed prospectively in 694 patients treated with

  11. Prospective Study on Incidence, Risk Factors, and Long-Term Outcome of Osteonecrosis in Pediatric Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    Winkel, Mariel L. Te; Pieters, Rob; Hop, Wim C. J.; de Groot-Kruseman, Hester A.; Lequin, Maarten H.; van der Sluis, Inge M.; Bokkerink, Jos P. M.; Leeuw, Jan A.; Bruin, Marrie C. A.; Egeler, R. Maarten; Veerman, Anjo J. P.; van den Heuvel-Eibrink, Marry M.

    2011-01-01

    Purpose We studied cumulative incidence, risk factors, therapeutic strategies, and outcome of symptomatic osteonecrosis in pediatric patients with acute lymphoblastic leukemia (ALL). Patients and Methods Cumulative incidence of osteonecrosis was assessed prospectively in 694 patients treated with th

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

    NARCIS (Netherlands)

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

    2002-01-01

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

  13. Obesity and survival in a cohort of predominantly Hispanic children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Baillargeon, Jacques; Langevin, Anne-Marie; Lewis, Margaret; Estrada, Jaime; Mullins, Judith; Pitney, Aaron; Ma, Jennie Z; Chisholm, Gary B; Pollock, Brad H

    2006-09-01

    Acute lymphoblastic leukemia (ALL), the most common malignancy in children, constitutes 25% of all pediatric cancer. Childhood cancer patients who are obese at diagnosis represent a particular challenge for the oncologist. Obesity may complicate chemotherapy dose determination, and has been associated with decreased overall and event-free survival in a number of adult cancer patients, and more recently in pediatric patients. The purpose of the present study was to examine whether obesity at diagnosis was associated with decreased overall and event-free survival in a cohort of 322 predominantly Hispanic pediatric patients with B-precursor ALL. Obesity was classified as an age-standardized and sex-standardized body mass index z-score at or above the 95th percentile. Hazard ratios (HRs) for overall and event-free survival were assessed using Cox proportional hazards regression modeling. Obesity at diagnosis was not associated with decreased overall survival (HR = 1.40, 95% confidence interval = 0.69-2.87) or event-free survival (HR = 1.08, 95% confidence interval = 0.65-1.82) in the overall cohort or in either of the 2 age-at-diagnosis (2 to 9 y; 10 to 18 y) subgroups. Our finding of no obesity-related prognostic effect in the overall cohort and in the under 2 to 9-year age-at-diagnosis cohort was consistent with the previous large-scale study of ALL patients; the absence of a prognostic effect in the 10 to 18-year age-at-diagnosis cohort, however, conflicted with previous findings.

  14. Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia.

    Science.gov (United States)

    Li, Yilong; Schwab, Claire; Ryan, Sarra L; Papaemmanuil, Elli; Robinson, Hazel M; Jacobs, Patricia; Moorman, Anthony V; Dyer, Sara; Borrow, Julian; Griffiths, Mike; Heerema, Nyla A; Carroll, Andrew J; Talley, Polly; Bown, Nick; Telford, Nick; Ross, Fiona M; Gaunt, Lorraine; McNally, Richard J Q; Young, Bryan D; Sinclair, Paul; Rand, Vikki; Teixeira, Manuel R; Joseph, Olivia; Robinson, Ben; Maddison, Mark; Dastugue, Nicole; Vandenberghe, Peter; Haferlach, Claudia; Stephens, Philip J; Cheng, Jiqiu; Van Loo, Peter; Stratton, Michael R; Campbell, Peter J; Harrison, Christine J

    2014-04-03

    Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes.

  15. ALL-2005方案对儿童急性淋巴细胞白血病髓外白血病防治效果分析%Analysis of prevention and therapeutic effectiveness of extramedullary leukemia in children with childhood acute lymphoblastic leukemia with ALL-2005 protocol

    Institute of Scientific and Technical Information of China (English)

    薛惠良; 顾龙君; 汤静燕; 陈静; 潘慈; 周敏; 董璐; 汤燕静; 王坚敏; 叶启东

    2012-01-01

    目的 总结ALL-2005方案对急性淋巴细胞白血病(ALL)患儿髓外白血病,包括中枢神经系统白血病(CNSL)及睾丸白血病(TL)的防治效果.方法 2005年5月-2008年5月共218例ALL患儿,采用ALL2005方案进行治疗,总结其临床及治疗情况.结果 218例ALL患儿中,5例初诊时伴CNSL,1例于诱导治疗期间发生CNSL,4例于维持治疗期间发生CNSL;1例初诊时伴TL发生,4例维持治疗期间发生TL.经治疗,2例CNSL患儿骨髓复发.其余8例均缓解至今;TL患儿1例骨髓复发,1例放弃治疗,3例缓解至今.结论 ALL2005方案疗效良好,有利于提高患儿长期生存质量.%Objective To analyze the prevention and therapeutic effectiveness of extramedullary leukemia including cen.ral nervous system leukemia ( CNSL) and testicular leukemia (TL) in children with childhood acute lymphoblastic leukemia (ALL) with ALL-2005 protocol. The clinical data were summarized. Methods From May 2005 to May 2008, 218 children with ALL were treated with All-2005 protocol. The clinical data were summarized. Results Five of 218 patients were found with CNSL and 1 with TL at the time of initial diagnosis of ALL, One child developed CNSL during treatment, 4 developed CNSL and 4 developed TL during maintenance treatment. After treatment , 2 patients with CNSL and 1 patient with TL relapsed; and 8 patients with CNSL and 3 patients with TL have been relieved and 1 patient with TL abandoned treatment. Conclusions ALL-2005 protocol shows good therapeutic effectiveness in treatment of children with ALL and improves the life quality of long term survival.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Daniel Willian Lustosa de Sousa

    2015-08-01

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

  18. 6-Thioguanine Induces Mitochondrial Dysfunction and Oxidative DNA Damage in Acute Lymphoblastic Leukemia Cells*

    OpenAIRE

    Zhang, Fan; Fu, Lijuan; Wang, Yinsheng

    2013-01-01

    Thiopurines are among the most successful chemotherapeutic agents used for treating various human diseases, including acute lymphoblastic leukemia and chronic inflammation. Although metabolic conversion and the subsequent incorporation of 6-thioguanine (SG) nucleotides into nucleic acids are considered important for allowing the thiopurine drugs to induce their cytotoxic effects, alternative mechanisms may also exist. We hypothesized that an unbiased analysis of SG-induced perturbation of the...

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

    OpenAIRE

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

    2013-01-01

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

  20. CYLD Regulates Noscapine Activity in Acute Lymphoblastic Leukemia via a Microtubule-Dependent Mechanism

    OpenAIRE

    Yang, Yunfan; Ran, Jie; Sun, Lei; Sun, Xiaodong; Luo, Youguang; Yan, Bing; Tala,; Liu, Min; Li, Dengwen; Zhang, Lei; Bao, Gang; Zhou, Jun

    2015-01-01

    Noscapine is an orally administrable drug used worldwide for cough suppression and has recently been demonstrated to disrupt microtubule dynamics and possess anticancer activity. However, the molecular mechanisms regulating noscapine activity remain poorly defined. Here we demonstrate that cylindromatosis (CYLD), a microtubule-associated tumor suppressor protein, modulates the activity of noscapine both in cell lines and in primary cells of acute lymphoblastic leukemia (ALL). Flow cytometry a...

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

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  3. Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia

    OpenAIRE

    Idalia Garza-Veloz; Margarita L. Martinez-Fierro; Jose Carlos Jaime-Perez; Karol Carrillo-Sanchez; Maria Guadalupe Ramos-Del Hoyo; Angel Lugo-Trampe; Augusto Rojas-Martinez; Cesar Homero Gutierrez-Aguirre; Oscar Gonzalez-Llano; Rosario Salazar-Riojas; Alfredo Hidalgo-Miranda; David Gomez-Almaguer; Rocio Ortiz-Lopez

    2015-01-01

    Background. Acute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL. Methods. 219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by...

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

    Science.gov (United States)

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

    2007-05-01

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

  5. Drugs under preclinical and clinical study for treatment of acute and chronic lymphoblastic leukemia

    OpenAIRE

    Jacob JA; Salmani JMM; Chen B

    2016-01-01

    Joe Antony Jacob, Jumah Masoud Mohammad Salmani, Baoan Chen Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China Abstract: Targeted therapy has modernized the treatment of both chronic and acute lymphoblastic leukemia. The introduction of monoclonal antibodies and combinational drugs has increased the survival rate of patients. Preclinical studies with various agents have resulted in positive outputs...

  6. In vivo response to methotrexate forecasts outcome of acute lymphoblastic leukemia and has a distinct gene expression profile.

    Directory of Open Access Journals (Sweden)

    Michael J Sorich

    2008-04-01

    Full Text Available Childhood acute lymphoblastic leukemia (ALL is the most common cancer in children, and can now be cured in approximately 80% of patients. Nevertheless, drug resistance is the major cause of treatment failure in children with ALL. The drug methotrexate (MTX, which is widely used to treat many human cancers, is used in essentially all treatment protocols worldwide for newly diagnosed ALL. Although MTX has been extensively studied for many years, relatively little is known about mechanisms of de novo resistance in primary cancer cells, including leukemia cells. This lack of knowledge is due in part to the fact that existing in vitro methods are not sufficiently reliable to permit assessment of MTX resistance in primary ALL cells. Therefore, we measured the in vivo antileukemic effects of MTX and identified genes whose expression differed significantly in patients with a good versus poor response to MTX.We utilized measures of decreased circulating leukemia cells of 293 newly diagnosed children after initial "up-front" in vivo MTX treatment (1 g/m(2 to elucidate interpatient differences in the antileukemic effects of MTX. To identify genomic determinants of these effects, we performed a genome-wide assessment of gene expression in primary ALL cells from 161 of these newly diagnosed children (1-18 y. We identified 48 genes and two cDNA clones whose expression was significantly related to the reduction of circulating leukemia cells after initial in vivo treatment with MTX. This finding was validated in an independent cohort of children with ALL. Furthermore, this measure of initial MTX in vivo response and the associated gene expression pattern were predictive of long-term disease-free survival (p < 0.001, p = 0.02.Together, these data provide new insights into the genomic basis of MTX resistance and interpatient differences in MTX response, pointing to new strategies to overcome MTX resistance in childhood ALL.Total XV, Therapy for Newly Diagnosed

  7. EBV, HCMV, HHV6, and HHV7 Screening in Bone Marrow Samples from Children with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Morales-Sánchez, A.; Pompa-Mera, E. N.; Fajardo-Gutiérrez, A.; Alvarez-Rodríguez, F. J.; Bekker-Méndez, V. C.; Flores-Chapa, J. de Diego; Flores-Lujano, J.; Jiménez-Hernández, E.; Peñaloza-González, J. G.; Rodríguez-Zepeda, M. C.; Torres-Nava, J. R.; Velázquez-Aviña, M. M.; Amador-Sánchez, R.; Alvarado-Ibarra, M.; Reyes-Zepeda, N.; Espinosa-Elizondo, R. M.; Pérez-Saldivar, M. L.; Núñez-Enríquez, J. C.; Mejía-Aranguré, J. M.; Fuentes-Pananá, E. M.

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood worldwide and Mexico has reported one of the highest incidence rates. An infectious etiology has been suggested and supported by epidemiological evidences; however, the identity of the involved agent(s) is not known. We considered that early transmitted lymphotropic herpes viruses were good candidates, since transforming mechanisms have been described for them and some are already associated with human cancers. In this study we interrogated the direct role of EBV, HCMV, HHV6, and HHV7 human herpes viruses in childhood ALL. Viral genomes were screened in 70 bone marrow samples from ALL patients through standard and a more sensitive nested PCR. Positive samples were detected only by nested PCR indicating a low level of infection. Our result argues that viral genomes were not present in all leukemic cells, and, hence, infection most likely was not part of the initial genetic lesions leading to ALL. The high statistical power of the study suggested that these agents are not involved in the genesis of ALL in Mexican children. Additional analysis showed that detected infections or coinfections were not associated with prognosis. PMID:25309913

  8. EBV, HCMV, HHV6, and HHV7 Screening in Bone Marrow Samples from Children with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    A. Morales-Sánchez

    2014-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is the most common cancer in childhood worldwide and Mexico has reported one of the highest incidence rates. An infectious etiology has been suggested and supported by epidemiological evidences; however, the identity of the involved agent(s is not known. We considered that early transmitted lymphotropic herpes viruses were good candidates, since transforming mechanisms have been described for them and some are already associated with human cancers. In this study we interrogated the direct role of EBV, HCMV, HHV6, and HHV7 human herpes viruses in childhood ALL. Viral genomes were screened in 70 bone marrow samples from ALL patients through standard and a more sensitive nested PCR. Positive samples were detected only by nested PCR indicating a low level of infection. Our result argues that viral genomes were not present in all leukemic cells, and, hence, infection most likely was not part of the initial genetic lesions leading to ALL. The high statistical power of the study suggested that these agents are not involved in the genesis of ALL in Mexican children. Additional analysis showed that detected infections or coinfections were not associated with prognosis.

  9. Pri-miR-34b/c rs4938723 polymorphism contributes to acute lymphoblastic leukemia susceptibility in Chinese children.

    Science.gov (United States)

    Tong, Na; Chu, Haiyan; Wang, Meilin; Xue, Yao; Du, Mulong; Lu, Lingling; Zhang, Heng; Wang, Feng; Fang, Yongjun; Li, Jie; Wu, Dongmei; Zhang, Zhengdong; Sheng, Xiaojing

    2016-01-01

    A polymorphism rs4938723 (T > C) within the promoter region of pri-miR-34b/c has been found to not only affect the expression of mature miR-34b/c but also contribute to the susceptibility to several cancer types. We designed a case-control study to evaluate the role of rs4938723 in childhood acute lymphoblastic leukemia (ALL). The rs4938723 CC genotype was significantly associated with reduced ALL risk (p = 0.003, ORadjusted = 0.51, 95% CI = 0.33-0.80 for CC vs. TT). Stratification analyses showed the differences were pronounced in older (> 6 years), male subjects, as well as in patients in low risk and T-ALL subtypes. The in vitro luciferase assays in Jurkat and K-562 cell lines showed that the transcription activity of miR-34b/c was increased when T allele transited to C allele (p < 0.05). In conclusion, rs4938723 genetic variant contributed to the susceptibility to Chinese childhood ALL by influencing the transcription activity of miR-34b/c promoter.

  10. PROGNOSTIC IMPACT OF WT-1 GENE EXPRESSION IN EGYPTIAN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA

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    Adel Abd Elhaleim Hagag

    2016-01-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common childhood cancer representing 23% of pediatric cancers. Wilms' tumor -1 gene has is a novel prognostic factor, minimal residual disease marker and therapeutic target in acute leukemia. Aim of the work: The aim of this work was to study the impact of WT-1 gene expression in prognosis of Egyptian children with ALL. Patients and methods: This study was conducted on 40 children with newly diagnosed ALL who were subjected to full history taking, thorough clinical examination and laboratory investigations including; complete blood count, LDH, BM aspiration, cytochemistry, immunophenotyping, assessment of WT-1 Gene by real time PCR in BM samples at time of diagnosis. Results: Positive WT-1 gene expression was found in 22 cases (55% and negative expression in 18 cases (45%. Positive WT-1 gene expression group (n=22 includes 14 males and 8 females with mean age at presentation of 5.261 ± 0.811 while negative WT-1 gene expression group (n=18 includes 12 males and 6 females with mean age at diagnosis of 9.669 ± 3.731 with significantly older age in negative WT-1 gene expression group but no significant differences between positive and negative WT-1 gene expression groups regarding sex and clinical presentations. There were no significant differences in platelets and WBCs counts, hemoglobin and LDH levels and number of peripheral blood and BM blast cells at diagnosis between positive and negative WT-1 gene expression groups but after induction therapy there were significantly lower BM blast cells in positive WT-1 gene expression group. There were no statistically significant differences between positive and negative WT-1 gene expression groups regarding immunophenotyping. There were significantly higher relapse and death rates and lower rates of CR, DFS and OAS in negativeWT-1 gene expression group.MRD at end of induction therapy was found in 14 cases out of 40 patients. There was

  11. Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

    Science.gov (United States)

    2016-09-29

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Acute Myeloid Leukemia

  12. Tumefactive intracranial presentation of precursor B-cell acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Forester, Craig M. [University of Utah, Salt Lake City, UT (United States); Braunreiter, Chi L. [University of Utah, Division of Pediatric Hematology Oncology, Primary Children' s Medical Center, Salt Lake City, UT (United States); Helen DeVos Children' s Hospital, Department of Pediatric Hematology Oncology, Grand Rapids, MI (United States); Yaish, Hasan; Afify, Zeinab [University of Utah, Division of Pediatric Hematology Oncology, Primary Children' s Medical Center, Salt Lake City, UT (United States); Hedlund, Gary L. [Primary Children' s Medical Center, Department of Pediatric Radiology, Salt Lake City, UT (United States)

    2009-11-15

    In children, leukemia is the most common malignancy, and approximately 75% of leukemias are acute lymphoblastic leukemia (ALL). Central nervous system leukemia is found at diagnosis in fewer than 5% of children with ALL. Leukemic intracranial masses have been described with acute myeloid leukemia, but ALL presenting as a mass lesion is rare. We describe a unique case of an intracranial confirmed precursor B cell (pre-B) ALL mass in a 13-year-old girl that was diagnosed by brain CT, MRI and cerebral angiography, and confirmed by biopsy. This report details pertinent history and distinguishing imaging features of an intracranial ALL tumefaction. (orig.)

  13. Chemo-sensitivity in a panel of B-cell precursor acute lymphoblastic leukemia cell lines, YCUB series, derived from children.

    Science.gov (United States)

    Goto, Hiroaki; Naruto, Takuya; Tanoshima, Reo; Kato, Hiromi; Yokosuka, Tomoko; Yanagimachi, Masakatsu; Fujii, Hisaki; Yokota, Shumpei; Komine, Hiromi

    2009-10-01

    Sensitivity to 10 anticancer drugs was evaluated in 6 childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cell lines. Authenticity of newly established cell lines was confirmed by genomic fingerprinting. The line YCUB-5R established at relapse was more resistant to 4-hydroperoxy-cyclophosphamide, cytarabine, L-asparaginase, topotecan, fludarabine, and etoposide than YCUB-5 from the same patient at diagnosis. Of the drugs tested, etoposide and SN-38 (irinotecan) showed highest efficacy in the panel, with 50% growth inhibition at 0.22-1.8 microg/ml and 0.57-3.6 ng/ml, respectively. This cell line panel offers an in vitro model for the development of new therapies for childhood BCP-ALL.

  14. Molecular evidence for central nervous system involvement in children with newly diagnosed acute lymphoblastic leukemia.

    Science.gov (United States)

    Januszkiewicz, D A; Nowak, J S

    1995-01-01

    Central nervous system (CNS) involvement in children with newly diagnosed acute lymphoblastic leukemia (ALL) would have profound implication for the prognosis and accurate stratification of CNS prophylactic therapy. Using PCR technique with specific primers for V, D and J segments of TCRD gene, the pattern of TCRD gene rearrangements in bone marrow lymphoblasts and in cells from cerebrospinal fluid (CSF) have been investigated. The study involved 21 children at the time of diagnosis with B-lineage ALL. In nine of 21 patients incomplete TCRDVD gene rearrangement has been found in CSF cells, which was identical to that observed in bone marrow of the same children. It can be concluded that at least in 43 per cent of all analysed cases, there were signs of CNS involvement in newly diagnosed ALL patients.

  15. PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome

    Science.gov (United States)

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  16. Risk group assignment differs for children and adults 1-45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol

    DEFF Research Database (Denmark)

    Toft, Nina; Birgens, Henrik; Abrahamsson, Jonas;

    2013-01-01

    The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined.......The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined....

  17. Pharmacogenetically based dosing of thiopurines in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Rotevatn, Elisabeth Orskov; Rosthøj, Susanne;

    2014-01-01

    therapy starting doses of 75 mg/m(2)/day. To reduce SMN risk, 6MP starting doses were reduced to 50 mg/m(2)/day for patients with TPMT heterozygosity in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2000 protocol. PROCEDURE: We explored the pattern of SMN and relapse in the NOPHO...

  18. Maintenance therapy of childhood acute lymphoblastic leukemia revisited

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Nersting, Jacob; Nielsen, Stine Nygaard;

    2016-01-01

    adjustment guidelines. PROCEDURE: To identify relapse predictors, we collected 28,255 data sets on drug doses and blood counts (median: 47/patient) and analyzed erythrocyte (Ery) levels of cytotoxic 6MP/MTX metabolites in 9,182 blood samples (median: 14 samples/patient) from 532 children on MTX/6MP...... maintenance therapy targeted to a white blood cell count (WBC) of 1.5-3.5 × 10(9) /l. RESULTS: After a median follow-up of 13.8 years for patients in remission, stepwise Cox regression analysis did not find age, average doses of 6MP and MTX, hemoglobin, absolute lymphocyte counts, thrombocyte counts, or Ery.......00-1.09], P = 0.048), the absolute neutrophil count (ANC; HR = 1.7 per 10(9) /l rise [1.3-2.4], P = 0.0007), and Ery thiopurine methyltransferase activity (HR = 2.7 per IU/ml rise [1.1-6.7], P = 0.03). WBC was significantly related to ANC (Spearman correlation coefficient, rs = 0.77; P

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

    Science.gov (United States)

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

    2002-11-01

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

  20. Simplified flow cytometric assay to detect minimal residual disease in childhood with acute lymphoblastic leukemia Detecção de doença residual mínima em crianças com leucemia linfoblástica aguda por citometria de fluxo

    Directory of Open Access Journals (Sweden)

    Elizabete Delbuono

    2008-08-01

    Full Text Available The detection of minimal residual disease (MRD is an important prognostic factor in childhood acute lymphoblastic leukemia (ALL providing crucial information on the response to treatment and risk of relapse. However, the high cost of these techniques restricts their use in countries with limited resources. Thus, we prospectively studied the use of flow cytometry (FC with a simplified 3-color assay and a limited antibody panel to detect MRD in the bone marrow (BM and peripheral blood (PB of children with ALL. BM and PB samples from 40 children with ALL were analyzed on days (d 14 and 28 during induction and in weeks 24-30 of maintenance therapy. Detectable MRD was defined as > 0.01% cells expressing the aberrant immunophenotype as characterized at diagnosis among total events in the sample. A total of 87% of the patients had an aberrant immunophenotype at diagnosis. On d14, 56% of the BM and 43% of the PB samples had detectable MRD. On d28, this decreased to 45% and 31%, respectively. The percentage of cells with the aberrant phenotype was similar in both BM and PB in T-ALL but about 10 times higher in the BM of patients with B-cell-precursor ALL. Moreover, MRD was detected in the BM of patients in complete morphological remission (44% on d14 and 39% on d28. MRD was not significantly associated to gender, age, initial white blood cell count or cell lineage. This FC assay is feasible, affordable and readily applicable to detect MRD in centers with limited resources.A detecção de doença residual mínima (DRM é um importante fator prognóstico na leucemia linfóide aguda (LLA infantil e fornece informações sobre a resposta ao tratamento e o risco de recaída. Entretanto, os altos custos das técnicas utilizadas limitam seu uso nos países em desenvolvimento. Desta forma, realizamos um estudo prospectivo para avaliar a citometria de fluxo (CF, utilizando três fluorescências e um painel limitado de anticorpos monoclonais, como método de detec

  1. Disseminated fusariosis and endogenous fungal endophthalmitis in acute lymphoblastic leukemia following platelet transfusion possibly due to transfusion-related immunomodulation

    Directory of Open Access Journals (Sweden)

    Yong Ku

    2011-11-01

    Full Text Available Abstract Background To report a case of disseminated fusariosis with endogenous endophthalmitis in a patient with acute lymphoblastic leukemia. Transfusion-associated immune modulation secondary to platelet transfusion could play an important role in the pathophysiology of this case. Case Presentation A 9 year-old male with acute lymphoblastic leukemia complicated by pancytopenia and disseminated Intravascular coagulation was given platelet transfusion. He developed disseminated fusariosis and was referred to the ophthalmology team for right endogenous endophthalmitis. The infection was controlled with aggressive systemic and intravitreal antifungals. Conclusion Patients with acute lymphoblastic leukemia are predisposed to endogenous fungal endophthalmitis. Transfusion-associated immune modulation may further increase host susceptibility to such opportunistic infections.

  2. [Local involvement of the optic nerve by acute lymphoblastic leukemia].

    Science.gov (United States)

    Bernardczyk-Meller, Jadwiga; Stefańska, Katarzyna

    2005-01-01

    The leucemias quite commonly involve the eyes and adnexa. In some cases it causes visual complants. Both, the anterior chamber of the eye and the posterior portion of the globe may sites of acute or chronic leukemia and leucemic relapse. We report an unique case of a 14 years old leucemic patient who suffered visual loss and papilloedema, due to a unilateral local involvement within optic nerve, during second relapse of acute lymphocytic leuemia. In spite of typical treatment of main disease, the boy had died. The authors present typical ophthalmic features of the leucemia, too.

  3. Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma: final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group

    Science.gov (United States)

    Labar, Boris; Suciu, Stefan; Willemze, Roel; Muus, Petra; Marie, Jean-Pierre; Fillet, Georges; Berneman, Zwi; Jaksic, Branimir; Feremans, Walter; Bron, Dominique; Sinnige, Harm; Mistrik, Martin; Vreugdenhil, Gerard; De Bock, Robrecht; Nemet, Damir; Gilotay, Caroline; Amadori, Sergio; de Witte, Theo

    2010-01-01

    Background Corticosteroids are a standard component of the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Our aim was to determine whether dexamethasone results in a better outcome than prednisolone. Design and Methods Adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma were randomized to receive, as part of their induction therapy on days 1–8 and 15–22, either dexamethasone 8 mg/m2 or prednisolone 60 mg/m2. Those who reached complete remission were given two courses of consolidation therapy with high-dose cytarabine and mitoxantrone and methotrexate and asparaginase. Subsequently patients younger than 50 years, with a suitable donor, were to undergo allogeneic stem cell transplantation, whereas the others were planned to receive either an autologous stem cell transplant or high-dose maintenance chemotherapy with prophylactic central nervous system irradiation. Randomization was done with a minimization technique. The primary endpoint was event-free survival and the analyses was conducted on an intention-to-treat basis. Results Between August 1995 and October 2003, 325 patients between 15 to 72 years of age were randomized to receive either dexamethasone (163 patients) or prednisolone (162 patients). After induction and the course of first consolidation therapy, 131 (80.4%) patients in the dexamethasone group and 124 (76.5%) in the prednisolone group achieved complete remission. No significant difference was observed between the two treatment groups with regards to 6-year event-free survival rates (±SE) which were 25.9% (3.6%) and 28.7% (3.5%) in the dexamethasone and prednisolone groups, respectively (P=0.82, hazard ratio 0.97; 95% confidence interval, 0.75–1.25). Disease-free survival after complete remission was also similar in the dexamethasone and prednisolone groups, the 6-year rates being 32.3% and 37.5%, respectively (hazard ratio 1.03; 95% confidence interval 0.76–1.40). The 6-year cumulative

  4. Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults

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    Lee KJ

    2016-08-01

    Full Text Available Kum Ja Lee,1 Vivian Chow,1 Ashley Weissman,2 Sunil Tulpule,3 Ibrahim Aldoss,4 Mojtaba Akhtari5 1Department of Clinical Pharmacy and Pharmaceutical Economics and Policy, University of Southern California, 2Department of Pharmacy, University of Southern California Norris Cancer Hospital, Los Angeles, CA, 3Department of Medicine, Raritan Bay Medical Center, Perth Amboy, NJ, 4Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, 5Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA Abstract: Adults with relapsed or refractory B-cell acute lymphoblastic leukemia have a dismal prognosis with a short median overall survival that can be measured in months. Because most patients will have chemotherapy-resistant disease, allogeneic hematopoietic stem cell transplantation remains the only potentially curative treatment. Despite advances in current management, patients continue to have poor outcomes and lack of durable responses. Thus, new therapies with alternative modes of actions are currently being investigated. Blinatumomab is a novel bispecific T-cell engager that simultaneously binds CD3-positive cytotoxic T-cells and CD19-positive B-cells, resulting in selective lysis of tumor cells. It has shown promising results in patients with relapsed or refractory acute lymphoblastic leukemia or those achieving hematologic response with persistent minimum residual disease. Future clinical trials will answer questions regarding its optimal place in the treatment paradigm. Dose-limiting toxicities include immunological toxicities and cytokine release syndrome. However, most patients tolerate the therapy relatively well. This review will focus on the pharmacology, clinical efficacy, and safety of blinatumomab in the treatment of adult B-cell acute lymphoblastic leukemia while highlighting its unique drug

  5. Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology

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    Bekker-Méndez Vilma

    2011-08-01

    Full Text Available Abstract Background Worldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in public hospitals in Mexico City. Methods Included in this study were those children, under 15 years of age and residents of Mexico City, who were diagnosed in 2006 and 2007 with leukemia, as determined by using the International Classification of Childhood Cancer. The average annual incidence rates (AAIR, and the standardized average annual incidence rates (SAAIR per million children were calculated. We calculated crude, age- and sex-specific incidence rates and adjusted for age by the direct method with the world population as standard. We determined if there were a correlation between the incidence of acute leukemias in the various boroughs of Mexico City and either the number of agricultural hectares, the average number of persons per household, or the municipal human development index for Mexico (used as a reference of socio-economic level. Results Although a total of 610 new cases of leukemia were registered during 2006-2007, only 228 fit the criteria for inclusion in this study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3; acute lymphoblastic leukemia (ALL was the most frequent type of leukemia, constituting 85.1% of the cases (SAAIR: 49.5 per million, followed by acute myeloblastic leukemia at 12.3% (SAAIR: 6.9 per million, and chronic myeloid leukemia at 1.7% (SAAIR: 0.9 per million. The 1-4 years age group had the highest SAAIR for ALL (77.7 per million. For cases of ALL, 73.2% had precursor B-cell immunophenotype (SAAIR: 35.8 per million and 12.4% had T-cell immunophenotype (SAAIR 6.3 per million. The peak ages for ALL were 2-6 years and 8-10 years. More than half the children (58.8% were

  6. Bacillus cereus catheter related bloodstream infection in a patient with acute lymphoblastic leukemia.

    Science.gov (United States)

    Gurler, N; Oksuz, L; Muftuoglu, M; Sargin, Fd; Besisik, Sk

    2012-01-01

    Bacillus cereus infection is rarely associated with actual infection and for this reason single positive blood culture is usually regarded as contamination . However it may cause a number of infections, such catheter-related bloodstream infections. Significant catheter-related bloodstream infections (CRBSI) caused by Bacillus spp. are mainly due to B. cereus and have been predominantly reported in immunocompromised hosts. Catheter removal is generally advised for management of infection. In this report, catheter-related bacteremia caused by B. cereus in a patient with acute lymphoblast c leukemia (ALL) in Istanbul Medical Faculty was presented.

  7. Successful Treatment of Fanconi Anemia and T-Cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Terrie Flatt

    2012-01-01

    Full Text Available Fanconi anemia is associated with an increased risk of malignancy. Patients are sensitive to the toxic effects of chemotherapy. We report the case of a patient with Fanconi anemia who developed T-cell acute lymphoblastic leukemia. He experienced chemotherapy-related complications including prolonged neutropenia, grade IV vincristine neuropathy, and disseminated aspergillosis. He was successfully treated with modified dosing of cytarabine and intrathecal methotrexate followed by allogeneic bone marrow transplant. The aspergillosis was treated with systemic antifungal treatment and surgical resection. Now 30 months after bone marrow transplant the patient is without evidence of aspergillosis or leukemia.

  8. Trigeminal nerve involvement in T-cell acute lymphoblastic leukemia: value of MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Karadag, Demet; Karaguelle, Ayse Tuba; Erden, Ilhan; Erden, Ayse E-mail: erden@ada.net.tr

    2002-10-01

    A 30-year-old male with T-cell acute lymphoblastic leukemia presented with facial numbness. Neurological examination revealed paresthesia of the left trigeminal nerve. Cerebrospinal fluid (CSF) cytology showed no atypical cells. Gadolinium-enhanced magnetic resonance (MR) imaging demonstrated enlargement and enhancement of intracranial portions of the left trigeminal nerve. The abnormal MR imaging findings almost completely resolved after the chemotherapy. Gadolinium-enhanced MR imaging is not only a useful procedure for the early diagnosis of cranial nerve invasion by leukemia but it might be helpful to follow the changes after the treatment.

  9. Testicular involvement in acute lymphoblastic leukemia. Consequences of radiotherapy and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Brauner, R.; Czernichow, P.; Rappaport, R.; Schaison, G.

    1986-06-05

    Acute lymphoblastic leukemia has a higher mortality rate in boys as a result of possible testicular involvement; indeed, the testicle is the site of initial relapse in 6% of cases and is involved in 15% of all cases. Clinical diagnosis of testicular involvement is usually readily established. Treatment is delivery of 24 grays to both testicles and intensification of chemotherapy. In children who recover from their leukemia, this irradiation produces not only destruction of germ cells but also endocrine impairment which should be looked for and treated; replacement therapy with slow-action testosterone will be combined with the other hormonal treatments which pituitary deficiencies secondary to cranial irradiation may require.

  10. FACIAL PALSY AS FIRST PRESENTATION OF ACUTE LYMPHOBLASTIC LEUKEMIA: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    S. Inaloo

    2008-11-01

    Full Text Available ObjectiveFacial paralysis in children is very often idiopathic and isolated facial nerve palsy, resulting from leukemic infiltration is a rare occurrence. Here we present the case of a 14 year-old boy with acute lymphobastic leukemia, who first presented with isolated right side peripheral facial nerve paralysis and was initially diagnosed with Bell's palsy.ConclusionThe presence of Bell's palsy in young children requires a complete evaluation, keeping in mind the possibility of leptomeningeal disease.Key words: Lymphoblastic Leukemia, Facial nerve palsy, Children.

  11. Acute lymphoblastic leukemia in children with associated genetic conditions other than Down's syndrome. The AIEOP experience.

    Science.gov (United States)

    Ziino, Ottavio; Rondelli, Roberto; Micalizzi, Concetta; Luciani, Matteo; Conter, Valentino; Aricò, Maurizio

    2006-01-01

    We retrospectively reviewed the databases of seven studies on acute lymphoblastic leukemia (ALL) by the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) to identify patients with associated genetic disease, other than Down's syndrome. Forty-two patients were reported to have associated genetic conditions that included beta-thalassemia (n=10), ataxia-telangiectasia (n=5), neurofibromatosis (n=3), Sotos syndrome (n=2) and other individual conditions. Patients with ataxia-telangiectasia, all with T-cell ALL, had a higher frequency of adverse events.

  12. Suppressed spontaneous secretion of growth hormone in girls after treatment for acute lymphoblastic leukaemia.

    OpenAIRE

    Moëll, C; Garwicz, S; Westgren, U; Wiebe, T; Albertsson-Wikland, K.

    1989-01-01

    The spontaneous secretion of growth hormone during a 24 hour period and the response of growth hormone to growth hormone releasing hormone was studied in 13 girls who had received treatment for acute lymphoblastic leukemia that included cranial irradiation with 20-24 Gy in 12-14 fractions. At the time of investigation the girls were at varying stages of puberty and had normal concentrations of thyroid hormones. The mean interval between the end of treatment and investigation was 4.6 years. Th...

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    A very precise and reproducible polymerase chain reaction (PCR) method was developed in order to quantify minimal residual disease (MRD) in children with acute lymphoblastic leukaemia (ALL). A clone-specific competitor was constructed by introducing a restriction site in a PCR product identical...... under identical conditions. After restriction enzyme cleavage, the PCR products originating from the competitor and the malignant clone can be distinguished by size in a gel electrophoresis step and the amount of residual disease can be determined. The method is very sensitive with a detection limit...

  14. Vincristine-induced peripheral neuropathy in a neonate with congenital acute lymphoblastic leukemia.

    Science.gov (United States)

    Baker, Steven K; Lipson, David M

    2010-04-01

    We report the case of a 46-day-old boy with a fulminant vincristine-induced peripheral neuropathy after treatment for congenital acute lymphoblastic leukemia. Flaccid paralysis developed at the end of the first phase of induction, requiring intubation and ventilation for 51 days. Treatment was initiated with levocarnitine, N-acetylcysteine, and pyridoxine and progressive reversal of the neuropathy occurred over the next 4 months. Potential differences in pathogenesis and presentation of vincristine neurotoxicity and Guillian-Barre syndrome in the neonate are discussed.

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

    Science.gov (United States)

    Tomaszewska, B; Zoch-Zwierz, W M

    1995-11-01

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

  16. [Ribonuclease binase induces death in T-cell acute lymphoblastic leukemia cells by apoptosis].

    Science.gov (United States)

    Burnysheva, K M; Petrushanko, I Yu; Spirin, P V; Prassolov, V S; Makarov, A A; Mitkevich, V A

    2016-01-01

    Bacterial ribonuclease binase is a potential anticancer agent. In the present study, we have determined the toxic effect of binase towards cell lines of T-cell acute lymphoblastic leukemia Jurkat and CEMss. We have shown that binase induces apoptosis in these cells. At the same time, binase does not cause toxic effects in leukocytes of healthy donors, which suggests that binase activity towards leukemic cells is selective. We have found that the treatment of cancer cells with binase leads to a reduction in reactive oxygen species and transcription factor NFκB levels, and demonstrated that these effects are a common feature of the action of RNases on cancer cells.

  17. p16基因缺失在儿童与成人急性B淋巴细胞白血病的临床意义%Comparison of clinical implications of p16 deletion in childhood and adult B-lineage acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    肖小珍; 许娜; 张进芳; 曹睿; 黄园鹭; 肖雅娟; 高冠伦; 周璇; 魏永强

    2013-01-01

    clinical implications of p16 deletion in childhood and adult B-lineage acute lymphoblastic leukemia (B-ALL).Methods A total of 129 cases of de novo childhood (73 cases) and adult (56 cases) B-ALL were examined genetically and immunologically using G-banding techniqhe,interphase fluorescence in situ hybridization (I-FISH) and immunophenotyping by flow cytometry,and their clinical data were retrospectively analyzed.Results Of 73 childhood cases,the prevalences of homozygous deletion,hemizygous deletion and no deletion of p16 were 24.7% (18 cases),6.8% (5 cases) and 68.5% (50 cases) respectively,and of 56 adult cases,the incidences as of 14.3% (8cases),8.9% (5 cases) and 76.8% (43 cases) respectively.The incidence of p16 deletion between the two groups had no significant difference (P =0.338).In both groups,patients with or without p16 deletion had no significant difference in terms of white blood cells (WBC) count at diagnosis,BM blast percentage,chromosome karyotype,extra-infiltration and CRI rate.Of note,there were 2 cases,each in childhood and adult,showed no deletion at the time of diagnosis,their p16 deletions occurred at relapse.The deletion of p16 was associated with poor overall survival and event-free survival (EFS) in both childhood and adults.According to the standard of NCI risk stratification,we divided patients of two groups into standard and high risk category respectively,and performed further analysis.The significance of different risk category in children and adults was disparity.The overall survival (OS) rates of deletion and no deletion of p16 were 45.3%and 79.8% (P=0.006) in children,and 7.7% and 22.6% (P =0.002) in adults,respectively.EFS rates of deletion and no deletion of p16 were 33.5% and 58.1% (P =0.008) in children,and 0 and 10.9%(P < 0.01) in adults,respectively.Of the standard risk category in children,OS rates of deletion and no deletion of p1 6 were 46.8% and 89.3 % (P =0.015) respectively,and EFS rates of

  18. Pro-inflammatory-Related Loss of CXCL12 Niche Promotes Acute Lymphoblastic Leukemic Progression at the Expense of Normal Lymphopoiesis

    Science.gov (United States)

    Balandrán, Juan Carlos; Purizaca, Jessica; Enciso, Jennifer; Dozal, David; Sandoval, Antonio; Jiménez-Hernández, Elva; Alemán-Lazarini, Leticia; Perez-Koldenkova, Vadim; Quintela-Núñez del Prado, Henry; Rios de los Ríos, Jussara; Mayani, Héctor; Ortiz-Navarrete, Vianney; Guzman, Monica L.; Pelayo, Rosana

    2017-01-01

    Pediatric oncology, notably childhood acute lymphoblastic leukemia (ALL), is currently one of the health-leading concerns worldwide and a biomedical priority. Decreasing overall leukemia mortality in children requires a comprehensive understanding of its pathobiology. It is becoming clear that malignant cell-to-niche intercommunication and microenvironmental signals that control early cell fate decisions are critical for tumor progression. We show here that the mesenchymal stromal cell component of ALL bone marrow (BM) differ from its normal counterpart in a number of functional properties and may have a key role during leukemic development. A decreased proliferation potential, contrasting with the strong ability of producing pro-inflammatory cytokines and an aberrantly loss of CXCL12 and SCF, suggest that leukemic lymphoid niches in ALL BM are unique and may exclude normal hematopoiesis. Cell competence ex vivo assays within tridimensional coculture structures indicated a growth advantage of leukemic precursor cells and their niche remodeling ability by CXCL12 reduction, resulting in leukemic cell progression at the expense of normal niche-associated lymphopoiesis. PMID:28111575

  19. Thyroid Nodule in an Eighteen-Year-Old Man as the First Presentation of Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Valizadeh, Majid; Moghimi, Minoush; Feizi, Abdolamir; Radmand, Farbod; Piri, Zahra

    2014-01-01

    Introduction: Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood. Patients with ALL commonly present with easy bruising and infections due to medullary involvement. The extra medullary involvements of ALL manifests as hepatosplenomegaly, lymphadenopathy, and testicular enlargement. Among extramedullary manifestations of the ALL, thyroid involvement is rare. Herein, we reported a case of ALL that manifested as a thyroid nodule. Case Presentation: An 18-year-old young man with a thyroid nodule presented without any other symptom or sign. The excisional biopsy of the nodule was planned by the surgeon. After two months of lost to follow-up, the patient returned with a complaint of continuous bleeding after a tooth extraction. Peripheral blood smear (PBS) study and bone marrow aspiration proposed ALL and the flow cytometry confirmed the diagnosis. The R-Hyper-CVAD induction chemotherapeutic regimen (rituximab in combination with cyclophosphamide, vincristine, doxorubicin, and dexamethasone) was used for treatment. Interestingly, thyroid sonography and Tc99m scan showed resolution of the thyroid nodule after chemotherapy. Discussion: In this patient, poor interdisciplinary communication and the rarity of this manifestation led to a delayed diagnosis. Therefore, we insist on more careful clinical examinations, reassessment of unusual FNA reports, and closer communication between clinicians and pathologists in such cases. This approach would lead to accurate and earlier diagnosis and would prevent unnecessary interventions. PMID:25237325

  20. Somatic inactivation of ATM in hematopoietic cells predisposes mice to cyclin D3 dependent T cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Ehrlich, Lori A; Yang-Iott, Katherine; DeMicco, Amy; Bassing, Craig H

    2015-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of immature T cells that exhibits heterogeneity of oncogenic lesions, providing an obstacle for development of more effective and less toxic therapies. Inherited deficiency of ATM, a regulator of the cellular DNA damage response, predisposes young humans and mice to T-ALLs with clonal chromosome translocations. While acquired ATM mutation or deletion occurs in pediatric T-ALLs, the role of somatic ATM alterations in T-ALL pathogenesis remains unknown. We demonstrate here that somatic Atm inactivation in haematopoietic cells starting as these cells differentiate in utero predisposes mice to T-ALL at similar young ages and harboring analogous translocations as germline Atm-deficient mice. However, some T-ALLs from haematopoietic cell specific deletion of Atm were of more mature thymocytes, revealing that the developmental timing and celluar origin of Atm inactivation influences the phenotype of ATM-deficient T-ALLs. Although it has been hypothesized that ATM suppresses cancer by preventing deletion and inactivation of TP53, we find that Atm inhibits T-ALL independent of Tp53 deletion. Finally, we demonstrate that the Cyclin D3 protein that drives immature T cell proliferation is essential for transformation of Atm-deficient thymocytes. Our study establishes a pre-clinical model for pediatric T-ALLs with acquired ATM inactivation and identifies the cell cycle machinery as a therapeutic target for this aggressive childhood T-ALL subtype.

  1. Wntless (GPR177) expression correlates with poor prognosis in B-cell precursor acute lymphoblastic leukemia via Wnt signaling.

    Science.gov (United States)

    Chiou, Shyh-Shin; Wang, Li-Ting; Huang, Shih-Bo; Chai, Chee-Yin; Wang, Shen-Nien; Liao, Yu-Mei; Lin, Pei-Chin; Liu, Kwei-Yan; Hsu, Shih-Hsien

    2014-10-01

    B-cell precursor acute lymphoblastic leukemia (BCP ALL) is the most common childhood leukemia, with a cure rate of 80%. Nevertheless, disease relapse is the most important prognostic factor for the disease outcome. We aimed to elucidate the role of Wnt secretion-regulating protein, Wntless (Wls)/GPR177, on disease outcome in pediatric patients with BCP ALL, and assess its pathogenetic role in the regulation of the disease. Wls expression was characterized and correlated with Wnt pathway signaling in the bone marrow leukemia cells isolated from 44 pediatric patients with BCP ALL. The overexpression of Wls was detected in leukemia cells and was significantly correlated with the disease relapse and poor survival in the patients. The high expression of Wls also correlated with the Wnt expression and consequent downstream signaling activation, which was shown to provide essential proliferation, transformation and anti-apoptotic activity during leukemogenesis. These results indicated that Wls played an essential role in disease relapse and poor survival in patients with BCP ALL. Therefore, Wls may provide a potential future therapeutic target, particularly for patients who do not respond to existing therapies and suffer relapse.

  2. Preservation of high glycolytic phenotype by establishing new acute lymphoblastic leukemia cell lines at physiologic oxygen concentration

    Energy Technology Data Exchange (ETDEWEB)

    Sheard, Michael A., E-mail: msheard@chla.usc.edu [Developmental Therapeutics Program, USC-CHLA Institute for Pediatric Clinical Research, Division of Hematology-Oncology, Children' s Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027 (United States); Ghent, Matthew V., E-mail: mattghent@gmail.com [Department of Pathology, Keck School of Medicine, University of Southern California, Health Sciences Campus, Los Angeles, CA 90089 (United States); Cabral, Daniel J., E-mail: dcabral14@gmail.com [Cancer Center and Departments of Cell Biology & Biochemistry, Pharmacology & Neuroscience, Internal Medicine and Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430 (United States); Lee, Joanne C., E-mail: joannebarnhart@gmail.com [Cancer Center and Departments of Cell Biology & Biochemistry, Pharmacology & Neuroscience, Internal Medicine and Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430 (United States); Khankaldyyan, Vazgen, E-mail: khangaldian@yahoo.com [Developmental Therapeutics Program, USC-CHLA Institute for Pediatric Clinical Research, Division of Hematology-Oncology, Children' s Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027 (United States); Ji, Lingyun, E-mail: lingyun.ji@med.usc.edu [Developmental Therapeutics Program, USC-CHLA Institute for Pediatric Clinical Research, Division of Hematology-Oncology, Children' s Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027 (United States); Wu, Samuel Q., E-mail: swu@chla.usc.edu [Medical Genetics, Children' s Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027 (United States); Kang, Min H., E-mail: min.kang@ttuhsc.edu [Cancer Center and Departments of Cell Biology & Biochemistry, Pharmacology & Neuroscience, Internal Medicine and Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430 (United States); and others

    2015-05-15

    Cancer cells typically exhibit increased glycolysis and decreased mitochondrial oxidative phosphorylation, and they continue to exhibit some elevation in glycolysis even under aerobic conditions. However, it is unclear whether cancer cell lines employ a high level of glycolysis comparable to that of the original cancers from which they were derived, even if their culture conditions are changed to physiologically relevant oxygen concentrations. From three childhood acute lymphoblastic leukemia (ALL) patients we established three new pairs of cell lines in both atmospheric (20%) and physiologic (bone marrow level, 5%) oxygen concentrations. Cell lines established in 20% oxygen exhibited lower proliferation, survival, expression of glycolysis genes, glucose consumption, and lactate production. Interestingly, the effects of oxygen concentration used during cell line initiation were only partially reversible when established cell cultures were switched from one oxygen concentration to another for eight weeks. These observations indicate that ALL cell lines established at atmospheric oxygen concentration can exhibit relatively low levels of glycolysis and these levels are semi-permanent, suggesting that physiologic oxygen concentrations may be needed from the time of cell line initiation to preserve the high level of glycolysis commonly exhibited by leukemias in vivo. - Highlights: • Establishing new ALL cell lines in 5% oxygen resulted in higher glycolytic expression and function. • Establishing new ALL cell lines in 5% oxygen resulted in higher proliferation and lower cell death. • The divergent metabolic phenotypes selected in 5% and 20% oxygen are semi-permanent.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Bernard, N.; Alberdi, A.; Corona, A.; Guillosson, J.J.; Nafziger, J. [Universite Rene Descartes, Lab. d' Hematologie Cellulaire et Moleculaire, CNRS UMR 8147, Faculte de Pharmacie, 75 - Paris (France)

    2006-07-01

    Over the past 25 years, a possible association between exposure to extremely low frequency magnetic fields (50 Hz M.F.) and cancer has be en extensively studied. The most consistent data were found for B acute lymphoblastic leukaemia in children that represents the most common type of cancer encountered in childhood. However, controversial results were reported in epidemiologic studies about this potential adverse effect of 50 Hz M.F.. Therefore, we developed an animal model of B acute lymphoblastic leukaemia to investigate the possible co-initiating or promoting effects of 50 Hz M.F. on the incidence of leukaemia in children. In this model leukaemia was chemically induced in male W.K.A.H./H km rats by a nitrosourea derivative, N-butyl nitrosourea (B.N.U.) administered 5 days a week for 24 weeks. Development of leukaemia was monitored by clinical observation, follow-up of blood parameters and appearance of blasts cells in serially repeated peripheral blood samples. The phenotype of the leukaemia in the affected rats was determined by cytological examination and cytochemical reactions on blood and bone marrow cells and, by immuno phenotyping of bone marrow cells using various markers. Leukaemia occurred in 60% of B.N.U. treated rats. Among the leukemic rats, 65% developed B acute lymphoblastic leukaemia. The maximum of leukaemia development was observed between the 5. to the 8. month following the beginning of B.N.U. treatment. Using this model, we decided to investigate the potential co-initiating or promoting effects of 50 Hz M.F.. The possible effects of harmonics (150, 250 and 350 Hz) that pollute the electrical network are also studied. The total number of leukaemia and the phenotype of leukaemia obtained will be compared between the B.N.U. treated animals exposed to 50 Hz M.F. with or without harmonics and the animals treat ed with B.N.U. alone. We believe that the results of this experiment might be helpful to answer the question of whether or not 50 Hz M

  5. Hardware Segmentation on Digital Microscope Images for Acute Lymphoblastic Leukemia Diagnosis Using Xilinx System Generator

    Directory of Open Access Journals (Sweden)

    Prof. Kamal A. ElDahshan

    2014-09-01

    Full Text Available Image segmentation is considered the most critical step in image processing and helps to analyze, infer and make decisions especially in the medical field. Analyzing digital microscope images for earlier acute lymphoblastic leukemia diagnosis and treatment require sophisticated software and hardware systems. These systems must provide both highly accurate and extremely fast processing of large amounts of image data. In this work, the hardware segmentation framework for Acute Lymphoblastic Leukemia (ALL images based color histogram of Hue channel of HSV color space is proposed to segment each leukemia image into blasts and background using Field Programmable Gate Array (FPGA. The main purpose of this work is to implement image segmentation framework in a FPGA with minimum hardware resources and low execution time to be suitable enough for medical applications. Hardware framework of segmentation is designed using Xilinx System Generator (XSG as DSP design tool that enables the use of Simulink models, implemented in VHDL and synthesized for Xilinx SPARTAN-3E Starter kit (XC3S500E-FG320 FPGA.

  6. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia.

    Science.gov (United States)

    Zhang, Jinghui; Ding, Li; Holmfeldt, Linda; Wu, Gang; Heatley, Sue L; Payne-Turner, Debbie; Easton, John; Chen, Xiang; Wang, Jianmin; Rusch, Michael; Lu, Charles; Chen, Shann-Ching; Wei, Lei; Collins-Underwood, J Racquel; Ma, Jing; Roberts, Kathryn G; Pounds, Stanley B; Ulyanov, Anatoly; Becksfort, Jared; Gupta, Pankaj; Huether, Robert; Kriwacki, Richard W; Parker, Matthew; McGoldrick, Daniel J; Zhao, David; Alford, Daniel; Espy, Stephen; Bobba, Kiran Chand; Song, Guangchun; Pei, Deqing; Cheng, Cheng; Roberts, Stefan; Barbato, Michael I; Campana, Dario; Coustan-Smith, Elaine; Shurtleff, Sheila A; Raimondi, Susana C; Kleppe, Maria; Cools, Jan; Shimano, Kristin A; Hermiston, Michelle L; Doulatov, Sergei; Eppert, Kolja; Laurenti, Elisa; Notta, Faiyaz; Dick, John E; Basso, Giuseppe; Hunger, Stephen P; Loh, Mignon L; Devidas, Meenakshi; Wood, Brent; Winter, Stuart; Dunsmore, Kimberley P; Fulton, Robert S; Fulton, Lucinda L; Hong, Xin; Harris, Christopher C; Dooling, David J; Ochoa, Kerri; Johnson, Kimberly J; Obenauer, John C; Evans, William E; Pui, Ching-Hon; Naeve, Clayton W; Ley, Timothy J; Mardis, Elaine R; Wilson, Richard K; Downing, James R; Mullighan, Charles G

    2012-01-11

    Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.

  7. Acute isoniazid neurotoxicity in childhood.

    Science.gov (United States)

    Citak, Agop; Kaya, Ozlen; Uçsel, Raif; Karaböcüoğlu, Metin; Uzel, Nedret

    2002-01-01

    Acute isoniazid (INH) poisoning is uncommon in children. Although most physicians are aware of INH hepatotoxicity, acute INH poisoning and its treatment are not well recognized. INH is increasingly being used to control the spread of tuberculosis, and physicians should know its potentially fatal effects. INH overdose is known to result in rapid onset of seizures, metabolic acidosis and prolonged obtundation. We report two cases of obtundation secondary to INH overdose that was immediately reversed by pyridoxine. Parenteral pyridoxine administration is an effective method in INH intoxication. The intravenous form of pyridoxine must be available in the emergency care units, and INH toxicity should be suspected in any patient with refractory seizures and metabolic acidosis.

  8. 儿童急性淋巴细胞白血病诱导治疗结束时外周血淋巴细胞数与预后的关系%Prognostic value of absolute lymphocytes counts at the end of induction in childhood acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    黎巧茹; 柯志勇; 谭惠珍; 王丽娜; 罗学群; 黄礼彬

    2016-01-01

    Objective The objective of this study was to explore the prognostic value of absolute lymphocyte counts (ALC) at the end of induction in childhood acute lymphoblastic leukemia (ALL), and investigate its impact factors. Methods A retrospective study was carried out on the newly diagnosed childhood ALL younger than 16 years treated in pediatric department, the First Affiliated Hospital of Sun Yat-sen University from April 1, 2002 to March 31, 2013. The outcome and ALC at the end of induction were reviewed. ALC at the end of induction correlated with different risk classification , age, 5-year event free survival (EFS), cumulative incidence of relapse (CIR), and treatment related mortality (TRM) were studied. EFS and survival curves were estimated according to Kaplan-Meier method and compared by two tailed log-rank test. Cox regression proportional hazards model was used to analyze the possible prognostic factor. Results Totally, 348 cases of children with newly diagnosed ALL were analyzed. The 5-year EFS of patients in low ALC group (≤0.62×109/L) and high ALC group (>0.62×109/L) was (61.6±5.6)%and (81.8±1.5)%, respectively, and the difference had statistical significance. The 5 years CIR in low ALC group and high ALC group were (28.0±5.6)%and (15.3±2.4)%, and the TRM in low ALC group and high ALC group were (12.8±3.8)%and (2.9±1.1)%, respectively, and the difference had statistical significance. Only in the group of no more than 6 years old, 5-years EFS of low ALC group were inferior compared to those of high ALC group. Multivariate Cox regression analysis showed that, low ALC was an independent risk factor influencing the EFS of pediatric ALL in this study, risk ratio was 1.95, 95%CI (1.22,3.11). Conclusion Low ALC (≤0.62×109/L) at the end of induction was an independent factor for poor outcome in children with ALL, especially in non-high risk patients under 6 years old.%目的:分析儿童急性淋巴细胞白血病(ALL)诱导治疗结束时外

  9. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Sanjuan-Pla, Alejandra; Bueno, Clara; Prieto, Cristina; Acha, Pamela; Stam, Ronald W; Marschalek, Rolf; Menéndez, Pablo

    2015-12-17

    Infant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinical management and survival (∼85-90%) of childhood B-ALL, the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival infant B-ALL, t(4;11)+ patients harboring the fusion MLL-AF4 (MA4) display a particularly poor prognosis and a pro-B/mixed phenotype. Studies in monozygotic twins and archived blood spots have provided compelling evidence of a single cell of prenatal origin as the target for MA4 fusion, explaining the brief leukemia latency. Despite its aggressiveness and short latency, current progress on its etiology, pathogenesis, and cellular origin is limited as evidenced by the lack of mouse/human models recapitulating the disease phenotype/latency. We propose this is because infant cancer is from an etiologic and pathogenesis standpoint distinct from adult cancer and should be seen as a developmental disease. This is supported by whole-genome sequencing studies suggesting that opposite to the view of cancer as a "multiple-and-sequential-hit" model, t(4;11) alone might be sufficient to spawn leukemia. The stable genome of these patients suggests that, in infant developmental cancer, one "big-hit" might be sufficient for overt disease and supports a key contribution of epigenetics and a prenatal cell of origin during a critical developmental window of stem cell vulnerability in the leukemia pathogenesis. Here, we revisit the biology of t(4;11)+ infant B-ALL with an emphasis on its origin, genetics, and disease models.

  10. Synergism between the mTOR inhibitor rapamycin and FAK down-regulation in the treatment of acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Pei-Jie Shi

    2016-02-01

    Full Text Available Abstract Background Acute lymphoblastic leukemia (ALL is an aggressive malignant disorder of lymphoid progenitor cells in both children and adults. Although improvements in contemporary therapy and development of new treatment strategies have led to dramatic increases in the cure rate in children with ALL, the relapse rate remains high and the prognosis of relapsed childhood ALL is poor. Molecularly targeted therapies have emerged as the leading treatments in cancer therapy. Multi-cytotoxic drug regimens have achieved success, yet many studies addressing targeted therapies have focused on only one single agent. In this study, we attempted to investigate whether the effect of the mammalian target of rapamycin (mTOR inhibitor rapamycin is synergistic with the effect of focal adhesion kinase (FAK down-regulation in the treatment of ALL. Methods The effect of rapamycin combined with FAK down-regulation on cell proliferation, the cell cycle, and apoptosis was investigated in the human precursor B acute lymphoblastic leukemia cells REH and on survival time and leukemia progression in a non-obese diabetic/severe combined immunodeficiency (NOD/SCID mouse model. Results When combined with FAK down-regulation, rapamycin-induced suppression of cell proliferation, G0/G1 cell cycle arrest, and apoptosis were significantly enhanced. In addition, REH cell-injected NOD/SCID mice treated with rapamycin and a short-hairpin RNA (shRNA to down-regulate FAK had significantly longer survival times and slower leukemia progression compared with mice injected with REH-empty vector cells and treated with rapamycin. Moreover, the B-cell CLL/lymphoma-2 (BCL-2 gene family was shown to be involved in the enhancement, by combined treatment, of REH cell apoptosis. Conclusions FAK down-regulation enhanced the in vitro and in vivo inhibitory effects of rapamycin on REH cell growth, indicating that the simultaneous targeting of mTOR- and FAK-related pathways might offer a novel

  11. A televideo exercise and nutrition program for children with acute lymphoblastic leukemia in maintenance therapy: design and methods

    Directory of Open Access Journals (Sweden)

    Gibson CA

    2015-07-01

    Full Text Available Cheryl A Gibson,1 Keith J August,2 Jerry L Greene,3 Stephen D Herrmann,4 Jaehoon Lee,5 Susan P Harvey,6 Kate Lambourne,3 Debra K Sullivan7 1Department of Internal Medicine, Division of General and Geriatric Medicine, University of Kansas Medical Center, KS, USA; 2Children's Mercy Hospital, MO, USA; 3Department of Health, Sport, and Exercise Sciences, University of Kansas, KS, USA; 4Children's Health Research Center, Sanford Research, SD, USA; 5Institute for Measurement, Methodology, Analysis and Policy, Texas Tech University, TX, USA; 6Center for Research on Learning, University of Kansas, KS, USA; 7Department of Dietetics and Nutrition, University of Kansas Medical Center, KS, USA Abstract: Changes in nutrient intake and decreased exercise resulting from cancer therapies as well as their side effects may be contributing factors in the increased body weight and differences in physical fitness observed in survivors of childhood acute lymphoblastic leukemia (ALL. This article will describe the study protocol for an intervention program designed to improve the physical activity and nutrition behaviors of ALL survivors. Twenty-four children aged between 4 years and 12 years with ALL will be randomized to a 6-month technology-based exercise and nutrition program (TLC4ALLKids or to enhanced usual care (eUC. The participants randomized to the TLC4ALLKids will participate in weekly, 1-hour coaching sessions on nutrition and physical activity and 1-hour physical activity classes delivered by group video conferencing. Participants will be provided with iPad tablets loaded with video conferencing software and the Healthy Lifestyle Tracking calendar to track daily nutrition and physical activity goals and weight. Both groups will be provided with Fitbit™ Zip to monitor physical activity. To assess feasibility, participant recruitment (achievement of proposed sample size, attendance (per weekly online sessions/assessment sessions, and adherence (number of

  12. Relapse of acute lymphoblastic leukemia in the pancreas after bone marrow transplant

    Institute of Scientific and Technical Information of China (English)

    Guang-Xian Wang; Jun-Lin Liao; Dong Zhang; Li Wen

    2015-01-01

    Background: Relapse of acute lymphoblastic leukemia (ALL) in the pancreas is rare. We report a case of a 12-year-old boy who experienced a relapse of ALL in the pancreas after a bone marrow transplant. Methods: Clinical data, including course of illness, laboratory results, and imaging studies are included. The patient presented with acute pancreatitis, suspected to be secondary to gallstones, with ampullary obstruction. Ultrasound and magnetic resonance imaging demonstrated a distended gallbladder and intra- and extra-hepatic biliary dilatation with a cutoff at the pancreatic head, but with no evidence of gallstones. Results: Ultrasound-guided biopsy of the pancreas revealed ALL in the pancreas. Systematic chemotherapy was recommended, but was declined by the parents. The patient died one week later. Conclusion: Relapse of ALL in the pancreas is rare, but when a history of ALL is present, it should be considered in patients with pancreatic enlargement, obstructive jaundice, and pancreatitis.

  13. Results of external quality control study in flow cytometric acute lymphoblastic leukemia diagnostics

    Directory of Open Access Journals (Sweden)

    A. M. Popov

    2016-01-01

    Full Text Available Comparison of interpretation of acute lymphoblastic leukemia (ALL flow cytometric diagnostics data was the aim of the study. Immunophenotyping data obtained from 10 patients with ALL were analysed separately in 26 laboratories from Russian Federation and Kazahstan. Results comparison showed four main type of discordance: B-lineage ALL diagnostics during heavy bone marrow regeneration, great variability of T-ALL interpretation, complexity of ambiguous lineage acute leukemia and, finally, very different report types, unique for each laboratory. All these problems are the serious obstacles for standardization of flow cytometric ALL diagnostics in multicenter setting. Continuation of similar QC rounds following by consecutive discussions with further development of consensus diagnostic algorithm could be the first step for standardization of ALL immunophenotyping in Russian Federation and CIS countries.

  14. Serial Ultrasound Monitoring for Early Recognition of Asparaginase Associated Pancreatitis in Children With Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Raja, Raheel Altaf; Schmiegelow, K.; Henriksen, Birthe Merete;

    2015-01-01

    BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children and L-asparaginase is an essential component of the treatment. Cessation of L-asparaginase decreases event free survival. Acute pancreatitis is the toxicity that most commonly results in cessation of L...... protocol, with PEG-asparaginase of 2 or 6 week intervals, for 30 weeks had their pancreas monitored using serial ultrasound in order to detect early signs of inflammation. RESULTS: Nineteen of 31 eligible patients were included. Three of the included patients developed AAP. None of the patients, including...... the three patients that developed AAP, had signs of inflammatory edema or pancreas enzymes above three times the upper normal limit prior to AAP. CONCLUSION: We found no signs of inflammatory edema within the pancreas on ultrasound during treatment with PEG-asparginase in our cohort prior to development...

  15. Molecular-genetic insights in paediatric T-cell acute lymphoblastic leukaemia.

    Science.gov (United States)

    Van Vlierberghe, Pieter; Pieters, Rob; Beverloo, H Berna; Meijerink, Jules P P

    2008-10-01

    Paediatric T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive malignancy of thymocytes that accounts for about 15% of ALL cases and for which treatment outcome remains inferior compared to B-lineage acute leukaemias. In T-ALL, leukemic transformation of maturating thymocytes is caused by a multistep pathogenesis involving numerous genetic abnormalities that drive normal T-cells into uncontrolled cell growth and clonal expansion. This review provides an overview of the current knowledge on onco- and tumor suppressor genes in T-ALL and suggests a classification of these genetic defects into type A and type B abnormalities. Type A abnormalities may delineate distinct molecular-cytogenetic T-ALL subgroups, whereas type B abnormalities are found in all major T-ALL subgroups and synergize with these type A mutations during T-cell pathogenesis.

  16. The association between glucocorticoid therapy and BMI z-score changes in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Arpe, Marie-Louise Hyre; Rørvig, Sascha; Kok, Karin Bott;

    2015-01-01

    PURPOSE: Few studies have addressed the common issue of weight gain in children with acute lymphoblastic leukemia (ALL) during early phases of treatment, and even fewer have used the appropriate measure for weight fluctuation in children, BMI-for-age z-scores (BAZs). The purpose of this study...

  17. Acute lymphoblastic leukemia in children with Down syndrome: A retrospective analysis from the Ponte di Legno study group

    NARCIS (Netherlands)

    T.D. Buitenkamp (Trudy); S. Izraeli (Shai); M. Zimmermann (Martin); E. Forestier (Erik); N.A. Heerema (Nyla); M.M. van den Heuvel-Eibrink (Marry); R. Pieters (Rob); C.M. Korbijn (Carin); L.B. Silverman (Lewis); K. Schmiegelow (Kjeld); D.-C. Liang (Der-Cheng); K. Horibe (Keizo); M. Aricò (Maurizio); A. Biondi (Andrea); G. Basso (Giuseppe); K.R. Rabin (Karin); M. Schrappe (Martin); G. Cario (Gunnar); G. Mann (Georg); M. Morak (Maria); R. Panzer-Grümayer (Renate); V. Mondelaers (Veerle); T. Lammens (Tim); H. Cavé (Hèléne); B. Stark (Batia); I. Ganmore (Ithamar); A.V. Moorman (Anthony); A. Vora (Ajay); S.P. Hunger (Stephen); C.H. Pui (Ching-Hon); C.G. Mullighan (Charles); A. Manabe (Atsushi); G. Escherich (Gabriele); J.R. Kowalczyk (Jerzy R.); J.A. Whitlock (James); C.M. Zwaan (Michel)

    2014-01-01

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

  18. Protracted and variable latency of acute lymphoblastic leukemia after TEL-AML1 gene fusion in utero

    NARCIS (Netherlands)

    Wiemels, JL; Ford, AM; Van Wering, ER; Postma, A; Greaves, M

    1999-01-01

    We report a pair of identical twins with concordant acute lymphoblastic leukemia (ALL). Unusually, their diagnoses were spaced 9 years apart at ages 5 and 14, Leukemic cells in both twins had a TEL-AML1 rearrangement, which was characterized at the DNA level by an adaptation of a long distance polym

  19. Variation in survival of European children with acute lymphoblastic leukaemia, diagnosed in 1978-1992 : the EUROCARE study

    NARCIS (Netherlands)

    Coebergh, JW; Pastore, G; Gatta, G; Corazziari, [No Value; Kamps, W

    2001-01-01

    The aim of this study was to provide a comparative description of geographical variations and time trends in the population-based survival of European children with acute lymphoblastic leukaemia (ALL). Data on 13 344 newly diagnosed children (0-14 years) with ALL were included in the EUROCARE study

  20. Precursor T-cell acute lymphoblastic leukemia presenting with bone marrow necrosis: a case report

    Directory of Open Access Journals (Sweden)

    Khoshnaw Najmaddin SH

    2012-10-01

    Full Text Available Abstract Introduction Bone marrow necrosis is a clinicopathological condition diagnosed most often at postmortem examination, but it is also seen during the course of malignancy and is not always associated with a poor prognosis. The morphological features of bone marrow necrosis are disruption of the normal marrow architecture and necrosis of myeloid tissue and medullary stroma. Non-malignant conditions associated with bone marrow necrosis are sickle cell anemia, infections, drugs (sulfasalazine, interferon α, all-trans retinoic acid, granulocyte colony-stimulating factor and fludarabine, disseminated intravascular coagulation, antiphospholipid antibody syndrome and acute graft versus host diseases. The malignant causes are leukemia, lymphoma and metastatic carcinomas. Herein we report the case of a patient with precursor T-cell acute lymphoblastic leukemia and bone marrow necrosis at initial presentation. Case presentation A 10-year-old Kurdish boy was presented with generalized bone pain and fever of 1 month’s duration which was associated with sweating, easy fatigability, nose bleeding, breathlessness and severe weight loss. On examination, we observed pallor, tachypnea, tachycardia, low blood pressure, fever, petechial hemorrhage, ecchymoses, tortuous dilated veins over the chest and upper part of abdomen, multiple small cervical lymph node enlargements, mildly enlarged spleen, palpable liver and gross abdominal distention. Blood analysis revealed pancytopenia and elevated lactate dehydrogenase and erythrocyte sedimentation rate. Imaging results showed mediastinal widening on a planar chest X-ray and diffuse focal infiltration of the axial bone marrow on magnetic resonance imaging of the lumbosacral vertebrae. Bone marrow aspiration and biopsy examination showed extensive bone marrow necrosis. Immunophenotyping analysis of the bone marrow biopsy confirmed T-cell acute lymphoblastic leukemia, as CD3 and terminal deoxynucleotidyl

  1. [The feasibility of Erwinia asparaginase for pediatric patients who developed an allergic reaction to E.coli asparaginase during treatment of acute lymphoblastic leukemia].

    Science.gov (United States)

    Takahashi, Hiroyoshi; Koh, Katsuyoshi; Kato, Motohiro; Isobe, Kiyotaka; Yasui, Naoko; Mori, Makiko; Akiyama, Kosuke; Kikuchi, Akira; Hanada, Ryoji

    2013-04-01

    Asparaginase (ASNase) is one of the most important key drugs in the treatment of acute lymphoblastic leukemia (ALL). However, clinical hypersensitivity reactions often occur and lead to the discontinuation of ASNase treatment. Here, we report a retrospective study of 68 Erwinia ASNase (Erw-ASNase) administrations in 11 patients with childhood ALL who developed allergic reactions to E.coli-ASNase in our hospital between 2006 and 2012. The median age of the patients was 6 (range, 0 to 14). Erw-ASNase purchased overseas by the patients' guardians had already been administered when we obtained informed consent from the guardians. In all patients, fibrinogen and/or anti-thrombin III levels were decreased, but thrombosis did not develop. There was only one mild adverse event (grade 2 urticaria) in one patient, in whom Erw-ASNase could be continued after increasing the doses of premedication with antihistamine and prednisolone. Erw-ASNase could be safely administered to all patients.

  2. Concurrent acute myeloid leukemia and T lymphoblastic lymphoma in a patient with rearranged PDGFRB genes

    Directory of Open Access Journals (Sweden)

    Chang Hung

    2012-02-01

    Full Text Available Abstract Concurrent hematologic malignancies are relatively rare. We encountered a case of concurrent acute myeloid leukemia (AML and T lymphoblastic lymphoma. The bone marrow chromosome analysis showed the karyotype 46, XY, t(5;12(q33;p13, which indicated presence of PDGFRB gene translocations. Therefore, this disease belongs to the new WHO category of myeloid and lymphoid neoplasms with abnormalities in PDGFRA, PDGFRB and FGFR1 genes. Although such genetic mutations are prone to multi-lineage differentiation, the present case is in fact the first report of concurrent AML and T lymphoblastic lymphoma involving PDGFRB mutations. The patient was treated with cytarabine and daunomycin in combination with high dose dexamethasone. Allogeneic stem cell transplantation was performed after successful remission induction for both entities. The patient eventually died of chronic graft-versus-host-disease related infection. Based on such an experience, we suggest the decision of stem cell transplantation should be weighed carefully against the risks, especially when tyrosine kinase inhibitors are safe and potentially effective in dealing with such entities.

  3. Cannabis Extract Treatment for Terminal Acute Lymphoblastic Leukemia with a Philadelphia Chromosome Mutation

    Directory of Open Access Journals (Sweden)

    Yadvinder Singh

    2013-11-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a cancer of the white blood cells and is typically well treated with combination chemotherapy, with a remission state after 5 years of 94% in children and 30-40% in adults. To establish how aggressive the disease is, further chromosome testing is required to determine whether the cancer is myeloblastic and involves neutrophils, eosinophils or basophils, or lymphoblastic involving B or T lymphocytes. This case study is on a 14-year-old patient diagnosed with a very aggressive form of ALL (positive for the Philadelphia chromosome mutation. A standard bone marrow transplant, aggressive chemotherapy and radiation therapy were revoked, with treatment being deemed a failure after 34 months. Without any other solutions provided by conventional approaches aside from palliation, the family administered cannabinoid extracts orally to the patient. Cannabinoid resin extract is used as an effective treatment for ALL with a positive Philadelphia chromosome mutation and indications of dose-dependent disease control. The clinical observation in this study revealed a rapid dose-dependent correlation.

  4. Sulforaphane induces cell cycle arrest and apoptosis in acute lymphoblastic leukemia cells.

    Directory of Open Access Journals (Sweden)

    Koramit Suppipat

    Full Text Available Acute lymphoblastic leukemia (ALL is the most common hematological cancer in children. Although risk-adaptive therapy, CNS-directed chemotherapy, and supportive care have improved the survival of ALL patients, disease relapse is still the leading cause of cancer-related death in children. Therefore, new drugs are needed as frontline treatments in high-risk disease and as salvage agents in relapsed ALL. In this study, we report that purified sulforaphane, a natural isothiocyanate found in cruciferous vegetables, has anti-leukemic properties in a broad range of ALL cell lines and primary lymphoblasts from pediatric T-ALL and pre-B ALL patients. The treatment of ALL leukemic cells with sulforaphane resulted in dose-dependent apoptosis and G2/M cell cycle arrest, which was associated with the activation of caspases (3, 8, and 9, inactivation of PARP, p53-independent upregulation of p21(CIP1/WAF1, and inhibition of the Cdc2/Cyclin B1 complex. Interestingly, sulforaphane also inhibited the AKT and mTOR survival pathways in most of the tested cell lines by lowering the levels of both total and phosphorylated proteins. Finally, the administration of sulforaphane to the ALL xenograft models resulted in a reduction of tumor burden, particularly following oral administration, suggesting a potential role as an adjunctive agent to improve the therapeutic response in high-risk ALL patients with activated AKT signaling.

  5. Acute lymphoblastic leukemia presenting as a breast lump: A report of two cases

    Directory of Open Access Journals (Sweden)

    Syed Besina

    2013-01-01

    Full Text Available Extra-medullary leukemic infiltration of the breast by acute lymphoblastic leukemia (ALL is very rare. We report two cases of ALL presenting as breast masses and diagnosed on fine-needle aspiration (FNA. Our first patient, a post-partum 30-year-old female, developed bilateral breast lumps in her last trimester of pregnancy and complained of easy fatigability. Our second patient, a 14-year-old girl, presented with a right-breast lump of 1-week duration. She had received treatment for ALL 1 year back and had been in complete remission for the last 1 year. FNA of the breast nodules done in both the cases revealed diffuse infiltration by lymphoblasts. Subsequent hematological investigations confirmed bone marrow involvement by ALL in the first case and extra-medullary relapse in the second case. Fine-needle aspiration cytology (FNAC is an easy and cost effective method for the early diagnosis of metastatic leukemic infiltration, avoiding unnecessary excisional biopsies in such cases.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    with historical controls, we performed a retrospective national population-based study of adult ALL between 1998 and 2008. Patients were identified through the Danish Patobank and the Danish Cancer Registry; data was collected from patient files, and included 277 patients (median age, 47 years, range 15-91 years......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......). The 5-year projected event-free survival (pEFS(5y) ) and overall survival (pOS(5y) ) for the whole cohort was 27·5% [95% confidence interval (CI) 22·4-33·6] and 34·1% (95% CI 28·7-40·4), respectively. No patient above 65 years survived beyond 5 years from diagnosis. For patients receiving curatively...

  7. Cerebral venous thrombosis in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma during induction chemotherapy with l-asparaginase: The GRAALL experience.

    Science.gov (United States)

    Couturier, Marie-Anne; Huguet, Françoise; Chevallier, Patrice; Suarez, Felipe; Thomas, Xavier; Escoffre-Barbe, Martine; Cacheux, Victoria; Pignon, Jean-Michel; Bonmati, Caroline; Sanhes, Laurence; Bories, Pierre; Daguindau, Etienne; Dorvaux, Véronique; Reman, Oumedaly; Frayfer, Jamile; Orvain, Corentin; Lhéritier, Véronique; Ifrah, Norbert; Dombret, Hervé; Hunault-Berger, Mathilde; Tanguy-Schmidt, Aline

    2015-11-01

    Central nervous system (CNS) thrombotic events are a well-known complication of acute lymphoblastic leukemia (ALL) induction therapy, especially with treatments including l-asparaginase (l-ASP). Data on risk factors and clinical evolution is still lacking in adult patients. We report on the clinical evolution of 22 CNS venous thrombosis cases occurring in 708 adults treated for ALL or lymphoblastic lymphoma (LL) with the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-induction protocol, which included eight L-ASP (6,000 IU/m(2) ) infusions. The prevalence of CNS thrombosis was 3.1%. CNS thrombosis occurred after a median of 18 days (range: 11-31) when patients had received a median of three l-ASP injections (range: 2-7). Patients with CNS thrombosis exhibited a median antithrombin (AT) nadir of 47.5% (range: 36-67%) at Day 17 (range: D3-D28), and 95% of them exhibited AT levels lower than 60%. There were no evident increase in hereditary thrombotic risk factors prevalence, and thrombosis occurred despite heparin prophylaxis which was performed in 90% of patients. Acquired AT deficiency was frequently detected in patients with l-ASP-based therapy, and patients with CNS thrombosis received AT prophylaxis (45%) less frequently than patients without CNS thrombosis (83%), P = 0.0002). CNS thrombosis was lethal in 5% of patients, while 20% had persistent sequelae. One patient received all planned l-ASP infusions without recurrence of CNS thrombotic whereas l-ASP injections were discontinued in 20 patients during the management of thrombosis without a significant impact on overall survival (P = 0.4).

  8. MLL rearrangements in pediatric acute lymphoblastic and myeloblastic leukemias: MLL specific and lineage specific signatures

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    te Kronnie Geertruy

    2009-06-01

    Full Text Available Abstract Background The presence of MLL rearrangements in acute leukemia results in a complex number of biological modifications that still remain largely unexplained. Armstrong et al. proposed MLL rearrangement positive ALL as a distinct subgroup, separated from acute lymphoblastic (ALL and myeloblastic leukemia (AML, with a specific gene expression profile. Here we show that MLL, from both ALL and AML origin, share a signature identified by a small set of genes suggesting a common genetic disregulation that could be at the basis of mixed lineage leukemia in both phenotypes. Methods Using Affymetrix® HG-U133 Plus 2.0 platform, gene expression data from 140 (training set + 78 (test set ALL and AML patients with (24+13 and without (116+65 MLL rearrangements have been investigated performing class comparison (SAM and class prediction (PAM analyses. Results We identified a MLL translocation-specific (379 probes signature and a phenotype-specific (622 probes signature which have been tested using unsupervised methods. A final subset of 14 genes grants the characterization of acute leukemia patients with and without MLL rearrangements. Conclusion Our study demonstrated that a small subset of genes identifies MLL-specific rearrangements and clearly separates acute leukemia samples according to lineage origin. The subset included well-known genes and newly discovered markers that identified ALL and AML subgroups, with and without MLL rearrangements.

  9. RBP2 Promotes Adult Acute Lymphoblastic Leukemia by Upregulating BCL2.

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    Xiaoming Wang

    Full Text Available Despite recent increases in the cure rate of acute lymphoblastic leukemia (ALL, adult ALL remains a high-risk disease that exhibits a high relapse rate. In this study, we found that the histone demethylase retinoblastoma binding protein-2 (RBP2 was overexpressed in both on-going and relapse cases of adult ALL, which revealed that RBP2 overexpression was not only involved in the pathogenesis of ALL but that its overexpression might also be related to relapse of the disease. RBP2 knockdown induced apoptosis and attenuated leukemic cell viability. Our results demonstrated that BCL2 is a novel target of RBP2 and supported the notion of RBP2 being a regulator of BCL2 expression via directly binding to its promoter. As the role of RBP2 in regulating apoptosis was confirmed, RBP2 overexpression and activation of BCL2 might play important roles in ALL development and progression.

  10. X-linked agammaglobulinemia associated with B-precursor acute lymphoblastic leukemia.

    Science.gov (United States)

    Hoshino, Akihiro; Okuno, Yusuke; Migita, Masahiro; Ban, Hideki; Yang, Xi; Kiyokawa, Nobutaka; Adachi, Yuichi; Kojima, Seiji; Ohara, Osamu; Kanegane, Hirokazu

    2015-02-01

    X-linked agammaglobulinemia (XLA) is clinically characterized by reduced number of peripheral B cells and diminished levels of serum immunoglobulins, and caused by a mutation in the Bruton's tyrosine kinase (BTK) gene, which play a pivotal role in signal transduction of pre-B-cell receptor (BCR) and BCR. B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common malignancy in children, and it may be associated with gene alterations that regulate B-cell development. Here we described a first case of XLA associated BCP-ALL. The whole-exome sequencing revealed a somatic mutation in MLL2 in the sample from the onset of BCP-ALL. This study suggests that the alterations of BTK and MLL2 synergistically function as leukemogenesis.

  11. Genetic loss of SH2B3 in acute lymphoblastic leukemia

    Science.gov (United States)

    Perez-Garcia, Arianne; Ambesi-Impiombato, Alberto; Hadler, Michael; Rigo, Isaura; LeDuc, Charles A.; Kelly, Kara; Jalas, Chaim; Paietta, Elisabeth; Racevskis, Janis; Rowe, Jacob M.; Tallman, Martin S.; Paganin, Maddalena; Basso, Giuseppe; Tong, Wei; Chung, Wendy K.

    2013-01-01

    The SH2B adaptor protein 3 (SH2B3) gene encodes a negative regulator of cytokine signaling with a critical role in the homeostasis of hematopoietic stem cells and lymphoid progenitors. Here, we report the identification of germline homozygous SH2B3 mutations in 2 siblings affected with developmental delay and autoimmunity, one in whom B-precursor acute lymphoblastic leukemia (ALL) developed. Mechanistically, loss of SH2B3 increases Janus kinase-signal transducer and activator of transcription signaling, promotes lymphoid cell proliferation, and accelerates leukemia development in a mouse model of NOTCH1-induced ALL. Moreover, extended mutation analysis showed homozygous somatic mutations in SH2B3 in 2 of 167 ALLs analyzed. Overall, these results demonstrate a Knudson tumor suppressor role for SH2B3 in the pathogenesis of ALL and highlight a possible link between genetic predisposition factors in the pathogenesis of autoimmunity and leukemogenesis. PMID:23908464

  12. CYLD Regulates Noscapine Activity in Acute Lymphoblastic Leukemia via a Microtubule-Dependent Mechanism.

    Science.gov (United States)

    Yang, Yunfan; Ran, Jie; Sun, Lei; Sun, Xiaodong; Luo, Youguang; Yan, Bing; Tala; Liu, Min; Li, Dengwen; Zhang, Lei; Bao, Gang; Zhou, Jun

    2015-01-01

    Noscapine is an orally administrable drug used worldwide for cough suppression and has recently been demonstrated to disrupt microtubule dynamics and possess anticancer activity. However, the molecular mechanisms regulating noscapine activity remain poorly defined. Here we demonstrate that cylindromatosis (CYLD), a microtubule-associated tumor suppressor protein, modulates the activity of noscapine both in cell lines and in primary cells of acute lymphoblastic leukemia (ALL). Flow cytometry and immunofluorescence microscopy reveal that CYLD increases the ability of noscapine to induce mitotic arrest and apoptosis. Examination of cellular microtubules as well as in vitro assembled microtubules shows that CYLD enhances the effect of noscapine on microtubule polymerization. Microtubule cosedimentation and fluorescence titration assays further reveal that CYLD interacts with microtubule outer surface and promotes noscapine binding to microtubules. These findings thus demonstrate CYLD as a critical regulator of noscapine activity and have important implications for ALL treatment.

  13. A case of Schizophyllum commune sinusitis following unrelated cord blood transplantation for acute lymphoblastic leukemia.

    Science.gov (United States)

    Toya, Takashi; Shinohara, Akihito; Tatsuno, Keita; Seo, Sachiko; Nannya, Yasuhito; Ichikawa, Motoshi; Makimura, Koichi; Moriya, Kyoji; Kurokawa, Mineo

    2013-08-01

    Schizophyllum commune is a globally distributed basidiomycete fungus that is known as a rare cause of sinusitis, for which no prompt treatment has been established. We describe the first report of S. commune sinusitis following unrelated cord blood transplantation for acute lymphoblastic leukemia. Thirteen days after transplantation, a 23-year-old female developed maxillary and ethmoid sinusitis. The sinusitis was antimicrobial-resistant, and the sinus aspirate culture revealed white wooly mold, which was identified as S. commune by nucleotide sequencing. The patient was successfully treated with intravenous administration of liposomal amphotericin B for 2 months, followed by oral voriconazole. This report suggests the effectiveness of liposomal amphotericin B and voriconazole for S. commune infection in immunocompromised patients. Given the difficulty in distinguishing S. commune infection from aspergillosis by standard culture methods, the incidence of S. commune infection following allogeneic hematopoietic stem cell transplantation may be underestimated. Nucleotide sequencing may be useful in the diagnosis of S. commune infection.

  14. Chemotherapeutic treatment reduces circulating levels of surfactant protein-D in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Rathe, Mathias; Sorensen, Grith L; Wehner, Peder S;

    2016-01-01

    BACKGROUND: Surfactant protein D (SP-D) is a host defense molecule of the innate immune system that enhances pathogen clearance and modulates inflammatory responses. We hypothesized that circulating SP-D levels are associated with chemotherapy-induced mucositis and infectious morbidity in children...... with acute lymphoblastic leukemia (ALL). PROCEDURE: In a prospective study, 43 children receiving treatment for ALL were monitored for mucosal toxicity from diagnosis through the induction phase of treatment. Serial blood draws were taken to determine the levels of SP-D, interleukin-6 (IL-6), C......-reactive protein, and white blood cells. Data on fever, antibiotics, and bacteremia were collected. Baseline levels of circulating SP-D were compared with healthy controls. RESULTS: Baseline values of circulating SP-D were similar to levels in healthy controls (median: 829 ng/ml vs. 657 ng/ml, respectively, P > 0...

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

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    Dipo Samuel OLABUMUYI

    2011-10-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

  17. Population Analysis of Pharmacogenetic Polymorphisms Related to Acute Lymphoblastic Leukemia Drug Treatment

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    Marcela A. Chiabai

    2012-01-01

    Full Text Available This study aimed to evaluate in the Brazilian population, the genotypes and population frequencies of pharmacogenetic polymorphisms involved in the response to drugs used in treatment of acute lymphoblastic leukemia (ALL, and to compare the data with data from the HapMap populations. There was significant differentiation between most population pairs, but few associations between genetic ancestry and SNPs in the Brazilian population were observed. AMOVA analysis comparing the Brazilian population to all other populations retrieved from HapMap pointed to a genetic proximity with the European population. These associations point to preclusion of the use of genetic ancestry as a proxy for predicting drug response. In this way, any study aiming to correlate genotype with drug response in the Brazilian population should be based on pharmacogenetic SNP genotypes.

  18. RBP2 Promotes Adult Acute Lymphoblastic Leukemia by Upregulating BCL2

    Science.gov (United States)

    Wang, Xiaoming; Zhou, Minran; Fu, Yue; Sun, Ting; Chen, Jin; Qin, Xuemei; Yu, Yuan; Jia, Jihui; Chen, Chunyan

    2016-01-01

    Despite recent increases in the cure rate of acute lymphoblastic leukemia (ALL), adult ALL remains a high-risk disease that exhibits a high relapse rate. In this study, we found that the histone demethylase retinoblastoma binding protein-2 (RBP2) was overexpressed in both on-going and relapse cases of adult ALL, which revealed that RBP2 overexpression was not only involved in the pathogenesis of ALL but that its overexpression might also be related to relapse of the disease. RBP2 knockdown induced apoptosis and attenuated leukemic cell viability. Our results demonstrated that BCL2 is a novel target of RBP2 and supported the notion of RBP2 being a regulator of BCL2 expression via directly binding to its promoter. As the role of RBP2 in regulating apoptosis was confirmed, RBP2 overexpression and activation of BCL2 might play important roles in ALL development and progression. PMID:27008505

  19. Role of L-asparaginase in acute lymphoblastic leukemia: focus on adult patients

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    Rytting ME

    2012-06-01

    Full Text Available Michael E RyttingDepartment of Pediatrics and Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USAAbstract: Asparaginase preparations deplete asparagine in acute lymphoblastic leukemia (ALL blasts. Asparaginase in its various forms is an important component of treatment regimens for pediatric ALL. Recently, interest and use of asparaginase in adult patients with ALL has increased, particularly in young adults. There is much less information on asparaginase use and toxicity in adult compared with pediatric populations. This review surveys prior published studies of the three most commonly used asparagine preparations as used in adult patients, and discusses important toxicities encountered in adult patients who receive asparaginase preparations.Keywords: asparaginase, leukemia, adults, children

  20. Metastatic Calcinosis Cutis: A Case in a Child with Acute Pre-B Cell Lymphoblastic Leukemia

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    Juan Pablo Castanedo-Cázares

    2015-01-01

    Full Text Available Hypercalcemia in children with malignancy is an uncommon condition. It has been described in leukemia patients with impaired renal excretion of calcium or osteolytic lesions. Metastatic calcinosis cutis (MCC may develop if hypercalcemia persists. We report the case of a 5-year-old girl with an atypical dermatosis and unspecific gastrointestinal symptoms. Considered clinical diagnoses were xanthomas, histiocytosis, molluscum contagiosum, and nongenital warts. Cutaneous histological analysis showed amorphous basophilic deposits in the dermis suggestive of calcium deposits. Laboratory tests confirmed serum hypercalcemia. Extensive investigations such as bone marrow biopsy established the diagnosis of an acute pre-B cell lymphoblastic leukemia. Hypercalcemia in hematopoietic malignancies is unusual, especially as initial manifestation of the disease. Careful review of the literature fails to reveal previous reports of these peculiar cutaneous lesions of MCC in children with leukemia.

  1. Efficacy of Retinoids in IKZF1-Mutated BCR-ABL1 Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Churchman, Michelle L; Low, Jonathan; Qu, Chunxu; Paietta, Elisabeth M; Kasper, Lawryn H; Chang, Yunchao; Payne-Turner, Debbie; Althoff, Mark J; Song, Guangchun; Chen, Shann-Ching; Ma, Jing; Rusch, Michael; McGoldrick, Dan; Edmonson, Michael; Gupta, Pankaj; Wang, Yong-Dong; Caufield, William; Freeman, Burgess; Li, Lie; Panetta, John C; Baker, Sharyn; Yang, Yung-Li; Roberts, Kathryn G; McCastlain, Kelly; Iacobucci, Ilaria; Peters, Jennifer L; Centonze, Victoria E; Notta, Faiyaz; Dobson, Stephanie M; Zandi, Sasan; Dick, John E; Janke, Laura; Peng, Junmin; Kodali, Kiran; Pagala, Vishwajeeth; Min, Jaeki; Mayasundari, Anand; Williams, Richard T; Willman, Cheryl L; Rowe, Jacob; Luger, Selina; Dickins, Ross A; Guy, R Kiplin; Chen, Taosheng; Mullighan, Charles G

    2015-09-14

    Alterations of IKZF1, encoding the lymphoid transcription factor IKAROS, are a hallmark of high-risk acute lymphoblastic leukemia (ALL), however the role of IKZF1 alterations in ALL pathogenesis is poorly understood. Here, we show that in mouse models of BCR-ABL1 leukemia, Ikzf1 and Arf alterations synergistically promote the development of an aggressive lymphoid leukemia. Ikzf1 alterations result in acquisition of stem cell-like features, including self-renewal and increased bone marrow stromal adhesion. Retinoid receptor agonists reversed this phenotype, partly by inducing expression of IKZF1, resulting in abrogation of adhesion and self-renewal, cell cycle arrest, and attenuation of proliferation without direct cytotoxicity. Retinoids potentiated the activity of dasatinib in mouse and human BCR-ABL1 ALL, providing an additional therapeutic option in IKZF1-mutated ALL.

  2. Fatal Bacillus cereus endocarditis masquerading as an anthrax-like infection in a patient with acute lymphoblastic leukemia: case report.

    Science.gov (United States)

    Cone, Lawrence A; Dreisbach, Luke; Potts, Barbara E; Comess, Barbara E; Burleigh, William A

    2005-01-01

    A 38-year-old male farm worker with relapsing acute lymphoblastic leukemia spontaneously developed an ulcerating ulcer on his anterior thigh which was surrounded by a non-tender area of erythema. Bacillus cereus was isolated from the ulcer and blood, and the patient received intravenous penicillin and vancomycin for one week. When sensitivity studies were returned he was treated with gatifloxacin orally. After two weeks of combined antimicrobial therapy and negative blood cultures, the patient received combination chemotherapy with vincristine, prednisone, doxorubicin and cyclophosphamide. He was hospitalized a day after completing chemotherapy with neutropenic sepsis due to B. cereus. He received similar antimicrobial therapy as previously, but died three days later. At autopsy, the patient was found to have acute mitral valve endocarditis and bilateral brain abscesses. This was the first case of B. cereus endocarditis reported in a patient with acute lymphoblastic leukemia.

  3. Discrimination of acute lymphoblastic leukemia from systemic-onset juvenile idiopathic arthritis at disease onset

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    Mirian S. Tamashiro

    2011-01-01

    Full Text Available OBJECTIVE: To assess clinical and laboratory features that differentiate acute lymphoblastic leukemia from systemic juvenile idiopathic arthritis at disease onset. METHODS: Fifty-seven leukemia patients with musculoskeletal involvement, without blasts on peripheral blood and without glucocorticoid therapy at disease onset and 102 systemic juvenile idiopathic arthritis patients (International League of Associations for Rheumatology criteria were retrospectively evaluated. The following features were examined: fever, rheumatoid rash, arthritis, limb pain, hepatomegaly, splenomegaly, pericarditis, myocarditis, pleuritis, weight loss, bleeding, anemia, leukopenia, neutropenia, thrombocytopenia, erythrocyte sedimentation rate, and lactic dehydrogenase levels. RESULTS: The median age at disease onset was significantly higher in leukemia patients than in those with systemic-onset juvenile idiopathic arthritis (5.8 vs. 3.8 years. In addition, the frequencies of limb pain, hepatomegaly, weight loss and hemorrhagic manifestations were significantly higher in leukemia patients than in systemic-onset juvenile idiopathic arthritis patients (70% vs. 1%, 54% vs. 32%, 30% vs. 8%, and 9% vs. 0%, respectively. Likewise, the frequencies of anemia, leukopenia, neutropenia, thrombocytopenia and high lactic dehydrogenase levels were statistically higher in leukemia patients than in patients with systemic-onset juvenile idiopathic arthritis (88% vs. 57%, 39% vs. 1%, 60% vs. 1%, 77% vs. 1%, and 56% vs. 14%, respectively. Remarkably, multivariate analysis revealed that limb pain (OR = 553; 95% CI =46.48-6580.42 and thrombocytopenia (OR = 754.13; 95% CI =64.57-8806.72 were significant independent variables that differentiated leukemia from systemic-onset juvenile idiopathic arthritis. The R2 of the Nagelkerke test was 0.91, and the Kaplan-Meier survival curves were similar for acute lymphoblastic leukemia patients with and without limb pain. CONCLUSION: Our study

  4. Febrile neutropenia in children with acute lymphoblastic leukemia: single center experience

    Science.gov (United States)

    Özdemir, Nihal; Tüysüz, Gülen; Çelik, Nigar; Yantri, Leman; Erginöz, Ethem; Apak, Hilmi; Özkan, Alp; Yıldız, İnci; Celkan, Tiraje

    2016-01-01

    Aim: An important life-threatening complication of intensive chemotherapy administered in children with leukemia is febrile neutropenia. The objective of this study was to evaluate the clinical features and consequences of febrile neutropenia attacks in children who were treated for acute lymphoblastic leukemia. Material and Methods: Nighty-six children who received chemotherapy for acute lymphoblastic leukemia in our center between January 1995 and December 2010 were included in the study. The data related to demographic characteristics, treatment features, relapse and febrile neutropenia incidences, risk factors, culture results and prognosis were retrospectively evaluated from the patients’ files. Results: A total of two hundred-ninety nine febrile neutropenia attacks observed in the patients during initial treatment and relapse treatment were evaluated. When the incidence of febrile neutropenia was evaluated by years, it was observed that the patients treated after year 2000 had statistically significantly more febrile neutopenia attacks compared to the patients treated before year 2000. When the incidences of febrile neutropenia during initial treatment and during relapse treatment were compared, it was observed that more febrile neutropenia attacks occured during relapse treatment. Fifty-nine percent of all febrile neutropenia attacks were fever of unknown origin. Eighty microorganisms grew in cultures during febrile neutropenia throughout treatment in 75 patients; 86% were bacterial infections (50% gram positive and 50% gram negative), 8% were viral infections and 6% were fungal infections. Coagulase negative staphylococcus (n=17) was the most frequent gram positive pathogen; E. Coli (n=17) was the most commonly grown gram negative pathogen. Conclusions: In this study, it was found that an increase in the incidence of febrile neutropenia occured in years. Increments in treatment intensities increase the incidence of febrile neutropenia while improving

  5. Bacillus cereus bacteremia and multiple brain abscesses during acute lymphoblastic leukemia induction therapy.

    Science.gov (United States)

    Hansford, Jordan R; Phillips, Marianne; Cole, Catherine; Francis, Joshua; Blyth, Christopher C; Gottardo, Nicholas G

    2014-04-01

    Bacillus cereus can cause serious infections in immunosuppressed patients. This population may be susceptible to B. cereus pneumonia, bacteremia, cellulitis, and rarely cerebral abscess. Here we report an 8-year-old boy undergoing induction therapy for acute lymphoblastic leukemia who developed multifocal B. cereus cerebral abscesses, highlighting the propensity for B. cereus to develop cerebral abscesses. A review of the literature over the past 25 years identified another 11 cases (3 children and 8 adults) of B. cereus cerebral abscess in patients undergoing cancer therapy. B. cereus cerebral abscesses were associated with a high mortality rate (42%) and significant morbidity. Notably, B. cereus bacteremia with concomitant cerebral abscess was associated with induction chemotherapy for acute leukemia in both children and adults (10 of 12 case reports). Our case report and review of the literature highlights the propensity for B. cereus to develop cerebral abscess(es). Therefore, early consideration for neuroimaging should be given for any neutropenic cancer patient identified with B. cereus bacteremia, in particular those with acute leukemia during induction therapy.

  6. ZFX Controls Propagation and Prevents Differentiation of Acute T-Lymphoblastic and Myeloid Leukemia

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    Stuart P. Weisberg

    2014-02-01

    Full Text Available Tumor-propagating cells in acute leukemia maintain a stem/progenitor-like immature phenotype and proliferative capacity. Acute myeloid leukemia (AML and acute T-lymphoblastic leukemia (T-ALL originate from different lineages through distinct oncogenic events such as MLL fusions and Notch signaling, respectively. We found that Zfx, a transcription factor that controls hematopoietic stem cell self-renewal, controls the initiation and maintenance of AML caused by MLL-AF9 fusion and of T-ALL caused by Notch1 activation. In both leukemia types, Zfx prevents differentiation and activates gene sets characteristic of immature cells of the respective lineages. In addition, endogenous Zfx contributes to gene induction and transformation by Myc overexpression in myeloid progenitors. Key Zfx target genes include the mitochondrial enzymes Ptpmt1 and Idh2, whose overexpression partially rescues the propagation of Zfx-deficient AML. These results show that distinct leukemia types maintain their undifferentiated phenotype and self-renewal by exploiting a common stem-cell-related genetic regulator.

  7. The ability to cross the blood-cerebrospinal fluid barrier is a generic property of acute lymphoblastic leukemia blasts.

    Science.gov (United States)

    Williams, Mark T S; Yousafzai, Yasar M; Elder, Alex; Rehe, Klaus; Bomken, Simon; Frishman-Levy, Liron; Tavor, Sigal; Sinclair, Paul; Dormon, Katie; Masic, Dino; Perry, Tracey; Weston, Victoria J; Kearns, Pamela; Blair, Helen; Russell, Lisa J; Heidenreich, Olaf; Irving, Julie A E; Izraeli, Shai; Vormoor, Josef; Graham, Gerard J; Halsey, Christina

    2016-04-21

    Prevention of central nervous system (CNS) relapse is critical for cure of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Despite this, mechanisms of CNS infiltration are poorly understood, and the timing, frequency, and properties of BCP-ALL blasts entering the CNS compartment are unknown. We investigated the CNS-engrafting potential of BCP-ALL cells xenotransplanted into immunodeficient NOD.Cg- ITALIC! Prkdc (ITALIC! scid) ITALIC! Il2rg (ITALIC! tm1Wjl)/SzJ mice. CNS engraftment was seen in 23 of 29 diagnostic samples (79%): 2 of 2 from patients with overt CNS disease and 21 of 27 from patients thought to be CNS negative by diagnostic lumbar puncture. Histologic findings mimic human pathology and demonstrate that leukemic cells transit the blood-cerebrospinal fluid barrier situated close to the dural sinuses, the site of recently discovered CNS lymphatics. Retrieval of blasts from the CNS showed no evidence for chemokine receptor-mediated selective trafficking. The high frequency of infiltration and lack of selective trafficking led us to postulate that CNS tropism is a generic property of leukemic cells. To test this, we performed serial dilution experiments which showed CNS engraftment in 5 of 6 mice after transplant of as few as 10 leukemic cells. Clonal tracking techniques confirmed the polyclonal nature of CNS-infiltrating cells, with multiple clones engrafting in both the CNS and periphery. Overall, these findings suggest that subclinical seeding of the CNS is likely to be present in most BCP-ALL patients at original diagnosis, and efforts to prevent CNS relapse should concentrate on effective eradication of disease from this site rather than targeting entry mechanisms.

  8. Modeling mechanisms of in vivo variability in methotrexate accumulation and folate pathway inhibition in acute lymphoblastic leukemia cells.

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    John C Panetta

    Full Text Available Methotrexate (MTX is widely used for the treatment of childhood acute lymphoblastic leukemia (ALL. The accumulation of MTX and its active metabolites, methotrexate polyglutamates (MTXPG, in ALL cells is an important determinant of its antileukemic effects. We studied 194 of 356 patients enrolled on St. Jude Total XV protocol for newly diagnosed ALL with the goal of characterizing the intracellular pharmacokinetics of MTXPG in leukemia cells; relating these pharmacokinetics to ALL lineage, ploidy and molecular subtype; and using a folate pathway model to simulate optimal treatment strategies. Serial MTX concentrations were measured in plasma and intracellular MTXPG concentrations were measured in circulating leukemia cells. A pharmacokinetic model was developed which accounted for the plasma disposition of MTX along with the transport and metabolism of MTXPG. In addition, a folate pathway model was adapted to simulate the effects of treatment strategies on the inhibition of de novo purine synthesis (DNPS. The intracellular MTXPG pharmacokinetic model parameters differed significantly by lineage, ploidy, and molecular subtypes of ALL. Folylpolyglutamate synthetase (FPGS activity was higher in B vs T lineage ALL (p<0.005, MTX influx and FPGS activity were higher in hyperdiploid vs non-hyperdiploid ALL (p<0.03, MTX influx and FPGS activity were lower in the t(12;21 (ETV6-RUNX1 subtype (p<0.05, and the ratio of FPGS to γ-glutamyl hydrolase (GGH activity was lower in the t(1;19 (TCF3-PBX1 subtype (p<0.03 than other genetic subtypes. In addition, the folate pathway model showed differential inhibition of DNPS relative to MTXPG accumulation, MTX dose, and schedule. This study has provided new insights into the intracellular disposition of MTX in leukemia cells and how it affects treatment efficacy.

  9. Inherited NUDT15 Variant Is a Genetic Determinant of Mercaptopurine Intolerance in Children With Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Yang, Jun J.; Landier, Wendy; Yang, Wenjian; Liu, Chengcheng; Hageman, Lindsey; Cheng, Cheng; Pei, Deqing; Chen, Yanjun; Crews, Kristine R.; Kornegay, Nancy; Wong, F. Lennie; Evans, William E.; Pui, Ching-Hon; Bhatia, Smita; Relling, Mary V.

    2015-01-01

    Purpose Mercaptopurine (MP) is the mainstay of curative therapy for acute lymphoblastic leukemia (ALL). We performed a genome-wide association study (GWAS) to identify comprehensively the genetic basis of MP intolerance in children with ALL. Patients and Methods The discovery GWAS and replication cohorts included 657 and 371 children from two prospective clinical trials. MP dose intensity was a marker for drug tolerance and toxicities and was defined as prescribed dose divided by the planned protocol dose during maintenance therapy; its association with genotype was evaluated using a linear mixed-effects model. Results MP dose intensity varied by race and ethnicity and was negatively correlated with East Asian genetic ancestry (P < .001). The GWAS revealed two genome-wide significant loci associated with dose intensity: rs1142345 in TPMT (Tyr240Cys, present in *3A and *3C variants; P = 8.6 × 10−9) and rs116855232 in NUDT15 (P = 8.8 × 10−9), with independent replication. Patients with TT genotype at rs116855232 were exquisitely sensitive to MP, with an average dose intensity of 8.3%, compared with those with TC and CC genotypes, who tolerated 63% and 83.5% of the planned dose, respectively. The NUDT15 variant was most common in East Asians and Hispanics, rare in Europeans, and not observed in Africans, contributing to ancestry-related differences in MP tolerance. Of children homozygous for either TPMT or NUDT15 variants or heterozygous for both, 100% required ≥ 50% MP dose reduction, compared with only 7.7% of others. Conclusion We describe a germline variant in NUDT15 strongly associated with MP intolerance in childhood ALL, which may have implications for treatment individualization in this disease. PMID:25624441

  10. NK Cell Genotype and Phenotype at Diagnosis of Acute Lymphoblastic Leukemia Correlate to Post-induction Residual Disease

    Science.gov (United States)

    Sullivan, Erin M.; Jeha, Sima; Kang, Guolian; Cheng, Cheng; Rooney, Barbara; Holladay, Martha; Bari, Rafijul; Schell, Sarah; Tuggle, MaCal; Pui, Ching-Hon; Leung, Wing

    2014-01-01

    Purpose Not all natural killer (NK) cells are equally cytotoxic against leukemia because of differences in receptor gene content and surface expression. We correlated NK cell genotype and phenotype at diagnosis of childhood acute lymphoblastic leukemia (ALL) with minimal residual disease (MRD) after induction chemotherapy. Experimental Design The NK cells and leukemia blasts of 244 patients were analyzed at diagnosis by killer-cell immunoglobulin-like receptor (KIR) typing and immunophenotyping. The results were correlated statistically to post-induction MRD status. Results The odds of being MRD positive in patients with KIR telomeric (Tel)-A/B genotype was 2.85 times the odds in those with Tel-A/A genotype (p=0.035). MRD positive patients were more likely to have KIR2DL5A (p=0.006) and expressed less activating receptor NKp46 and FASL on their NK cells (p=0.0074 and p=0.029, respectively). The odds of being MRD positive increased by 2.01-fold for every percentage increase in NK cells expressing KIR2DL1 in the presence of HLA-C2 ligand (p=0.034). The quantity of granzyme B inhibitor PI-9 in the leukemia blasts was greater in patients who were MRD positive (p=0.038). Collectively, five NK cell-related factors (Tel-B associated KIR2DL5A, NKp46, FASL, Granzyme B, and PI-9) are strongly associated with MRD positivity at the end of induction with 100% sensitivity and 80% specificity. Conclusions Our data support the hypothesis that NK cells with a strong effector phenotype in the setting of decreased leukemia resistance are associated with better leukemia control. PMID:25281696

  11. Detection of dicentric chromosome (9;20) in paediatric B-cell acute lymphoblastic leukaemia: prognostic significance.

    Science.gov (United States)

    Letouzey, Mathilde; Penther, Dominique; Roche-Lestienne, Catherine; Nelken, Brigitte; Devoldère, Catherine; Vannier, Jean-Pierre; Schneider, Pascale

    2015-02-01

    The dicentric chromosome (9;20) (dic(9;20)) is described in 2 % of childhood B-acute lymphoblastic leukaemia. Fluorescence in situ hybridization (FISH) is the most reliable method to identify dic(9;20) when compared with conventional cytogenetics. To define the prognostic importance of dic(9;20), we evaluated treatment response and patient survival. This was a retrospective study in three French university centres. Patients' clinical and laboratory characteristics and treatment response are described. Nine children with dic(9;20) have been identified since 1995. All patients had at least one poor prognostic feature either among the clinical features, the initial laboratory results or in the initial treatment response: central nervous system involvement (2/9), high median leucocyte count (≥50 G/L) (8/9) and poor response to prednisone (2/9). All patients were in complete cytological remission after induction therapy but only three had a good molecular response with minimal residual disease (MRD) <10(-3). Five out of nine patients relapsed and two died, 4 and 12 months after diagnosis, respectively. The event-free survival rate in this population was 44 % (95 % confidence interval (CI) = 0.09-0.79) and overall survival 78 % (95 % CI = 0.51-1.05). In this population, dic(9;20) is associated with a relatively poor prognosis. Patients showing dic(9;20), whether this cytogenetic abnormality is associated with other poor prognostic factors or not, should be identified at the outset in order to be offered a more intensive treatment protocol.

  12. Pharmacokinetics of 6-Thioguanine and 6-Mercaptopurine Combination Maintenance Therapy of Childhood ALL

    DEFF Research Database (Denmark)

    Nielsen, Stine N; Frandsen, Thomas L; Nersting, Jacob;

    2015-01-01

    Methotrexate/6-mercaptopurine maintenance therapy of childhood acute lymphoblastic leukemia is challenged by treatment-related hepatotoxicity, failure to achieve the myelosuppressive target, and lack of direct parameters for monitoring treatment efficacy or even intensity. Patients with low thiop...

  13. Targeting leukemia stem cells: which pathways drive self-renewal activity in T-cell acute lymphoblastic leukemia?

    OpenAIRE

    Belmonte, M; Hoofd, C.; Weng, A. P.; V. Giambra

    2016-01-01

    T-Cell acute lymphoblastic leukemia (t-all) is a malignancy of white blood cells, characterized by an uncontrolled accumulation of T-cell progenitors. During leukemic progression, immature T cells grow abnormally and crowd into the bone marrow, preventing it from making normal blood cells and spilling out into the bloodstream. Recent studies suggest that only discrete cell populations that possess the ability to recreate the entire tumour might be responsible for the initiation and propagatio...

  14. The NOTCH signaling pathway: role in the pathogenesis of T-cell acute lymphoblastic leukemia and implication for therapy

    OpenAIRE

    2013-01-01

    T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is characterized by aberrant activation of NOTCH1 in over 60% of T-ALL cases. The high prevalence of activating NOTCH1 mutations highlights the critical role of NOTCH signaling in the pathogenesis of this disease and has prompted the development of therapeutic approaches targeting the NOTCH signaling pathway. Small molecule gamma secretase inhibitors (GSIs) can effectively inhibit oncogenic NOTCH1 and are in clinical testing for the treatme...

  15. Cranial Radiation for Pediatric T-Lineage Acute Lymphoblastic Leukemia: A Systematic Review and Meta-analysis

    OpenAIRE

    Kelly, Michael J.; Thomas A. Trikalinos; Dahabreh, Issa J.; Gianferante, Matthew; Parsons, Susan K.

    2014-01-01

    There are heterogeneous approaches to cranial irradiation therapy (CRT) for T-lineage acute lymphoblastic leukemia (T-ALL). We performed a systematic review of studies that specified a radiation strategy and reported survival for pediatric T-ALL. Our analysis included 62 publications reporting 78 treatment groups (patient n=5844). The average event-free survival (EFS) was higher by 6% per 5 years (p

  16. Palonosetron for the prevention of nausea and vomiting in children with acute lymphoblastic leukemia treated with high dose methotrexate

    DEFF Research Database (Denmark)

    Nadaraja, Sambavy; Mamoudou, Aissata Diop; Thomassen, Harald;

    2012-01-01

    High dose methotrexate (HD-MTX), used in the treatment of children with acute lymphoblastic leukemia (ALL), is moderately emetogenic. First generation 5-HT(3) receptor antagonists are effective prophylactic agents but require multiple administrations. Palonosetron has a half life of 36-42 hours a...... of palonosetron (5 µg/kg) for the prevention of chemotherapy-induced nausea and vomiting in children 18 years of age with ALL treated with HD-MTX, 5 g/m(2)....

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

    Science.gov (United States)

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

    2009-02-01

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

  18. The prognosis of CALM-AF10-positive adult T-cell acute lymphoblastic leukemias depends on the stage of maturation arrest

    Science.gov (United States)

    Ben Abdelali, Raouf; Asnafi, Vahid; Petit, Arnaud; Micol, Jean-Baptiste; Callens, Céline; Villarese, Patrick; Delabesse, Eric; Reman, Oumedaly; Lepretre, Stephane; Cahn, Jean-Yves; Guillerm, Gaelle; Berthon, Céline; Gardin, Claude; Corront, Bernadette; Leguay, Thibaut; Béné, Marie-Christine; Ifrah, Norbert; Leverger, Guy; Dombret, Hervé; Macintyre, Elizabeth

    2013-01-01

    CALM-AF10 (also known as PICALM-MLLT10) is the commonest fusion protein in T-cell acute lymphoblastic leukemia, but its prognostic impact remains unclear. Molecular screening at diagnosis identified CALM-AF10 in 30/431 (7%) patients with T-cell acute lymphoblastic leukemia aged 16 years and over and in 15/234 (6%) of those aged up to 15 years. Adult CALM-AF10-positive patients were predominantly (72%) negative for surface (s)CD3/T-cell receptor, whereas children were predominantly (67%) positive for T-cell receptor. Among 22 adult CALM-AF10-positive patients treated according to the LALA94/GRAALL03-05 protocols, the poor prognosis for event-free survival (P=0.0017) and overall survival (P=0.0014) was restricted to the 15 T-cell receptor-negative cases. Among CALM-AF10-positive, T-cell receptor-negative patients, 82% had an early T-cell precursor phenotype, reported to be of poor prognosis in pediatric T-cell acute lymphoblastic leukemia. Early T-cell precursor acute lymphoblastic leukemia corresponded to 22% of adult LALA94/GRAALL03-05 T-cell acute lymphoblastic leukemias, but had no prognostic impact per se. CALM-AF10 fusion within early T-cell precursor acute lymphoblastic leukemia (21%) did, however, identify a group with a poor prognosis with regards to event-free survival (P=0.04). CALM-AF10 therefore identifies a poor prognostic group within sCD3/T-cell receptor negative adult T-cell acute lymphoblastic leukemias and is over-represented within early T-cell precursor acute lymphoblastic leukemias, in which it identifies patients in whom treatment is likely to fail. Its prognosis and overlap with early T-cell precursor acute lymphoblastic leukemia in pediatric T-cell acute lymphoblastic leukemia merits analysis. The clinical trial GRAALL was registered at Clinical Trials.gov number NCT00327678. PMID:23831922

  19. Medical neglect death due to acute lymphoblastic leukaemia: an autopsy case report.

    Science.gov (United States)

    Usumoto, Yosuke; Sameshima, Naomi; Tsuji, Akiko; Kudo, Keiko; Nishida, Naoki; Ikeda, Noriaki

    2014-12-01

    We report the case of 2-year-old girl who died of precursor B-cell acute lymphoblastic leukaemia (ALL), the most common cancer in children. She had no remarkable medical history. She was transferred to a hospital because of respiratory distress and died 4 hours after arrival. Two weeks before death, she had a fever of 39 degrees C, which subsided after the administration of a naturopathic herbal remedy. She developed jaundice 1 week before death, and her condition worsened on the day of death. Laboratory test results on admission showed a markedly elevated white blood cell count. Accordingly, the cause of death was suspected to be acute leukaemia. Forensic autopsy revealed the cause of death to be precursor B-cell ALL. With advancements in medical technology, the 5-year survival rate of children with ALL is nearly 90%. However, in this case, the deceased's parents preferred complementary and alternative medicine (i.e., naturopathy) to evidence-based medicine and had not taken her to a hospital for a medical check-up or immunisation since she was an infant. Thus, if she had received routine medical care, she would have a more than 60% chance of being alive 5 years after diagnosis. Therefore, we conclude that the parents should be accused of medical neglect regardless of their motives.

  20. A common genetic variation in CEBPE and acute lymphoblastic leukemia: a meta-analysis of the available evidence

    Directory of Open Access Journals (Sweden)

    Zhang XX

    2015-09-01

    Full Text Available Xiao-Xia Zhang,1,* Yue-Feng Du,2,* Ya-Jing Zhai,1 Fan Gao,3 Yu-Juan Yang,4 Xian-Cang Ma,3 Jun Lu,3 Jie Zheng31Department of Pharmacy, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Urology, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Clinical Research Center, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4The Third Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workAbstract: Acute lymphoblastic leukemia (ALL has been studied intensively for decades, but the details of its etiology and underlying mechanisms have yet to be fully elucidated. It is now generally acknowledged that genetic factors contribute greatly to the development of this disease. The gene encoding CCAAT/enhancer-binding protein ε (CEBPE is involved in the development of leukemia, and in particular the rs2239633 single nucleotide polymorphism (SNP of CEBPE. The association between rs2239633 and risk of ALL has been well studied, but remains unclear. Therefore, a meta-analysis was performed in this study to establish a more precise estimation of that relationship. A comprehensive literature search of the PubMed electronic database was conducted, and relevant studies published up to February 20, 2015 were selected for analysis. The references of the retrieved articles were also screened. The extracted data were analyzed statistically, and pooled odds ratios with 95% confidence intervals were calculated using Review Manager (version 5.2 to estimate the association strength. Finally, eleven studies were included in the meta-analysis. The pooled analyses revealed that rs2239633 was associated with an increased risk of childhood ALL in Caucasians under any contrast models (P<0

  1. Acute lymphoblastic leukemia subsequent to temozolomide use in a 26-year-old man: a case report

    Directory of Open Access Journals (Sweden)

    Shaikh Asim

    2010-08-01

    Full Text Available Abstract Introduction We report the development of acute lymphoblastic leukemia in a patient in whom temozolomide was used for the treatment of a brain tumor. Unlike that of other alkylating agents, the leukemogenic potential of temozolomide is considered to be very low, and very rarely are such cases reported. Case Presentation A 26-year-old Pakistani man who was treated for glioblastoma with temozolomide in an adjuvant setting was diagnosed to have acute lymphoblastic leukemia one year after stopping temozolomide. Conclusion Temozolomide is a highly active agent, used in the management of high-grade brain neoplasms. The agent is generally regarded to be safe, with an acceptable safety profile. Very few cases of myelodysplasia associated with temozolomide use have been reported. We report here the first case of acute lymphoblastic leukemia, which developed in a young man about one year after he finished taking temozolomide. This should provide further insight into a possible toxicity profile of this alkylating agent. This finding should be of interest to physicians in general and to medical oncologists in particular.

  2. Acute acquired comitant esotropia of childhood

    DEFF Research Database (Denmark)

    Hesgaard, Helena; Vinding, Troels

    2015-01-01

    acute onset of comitant esotropia, available data on ophthalmologic, orthoptic and neurologic examinations. Children with neurological signs, AACE recurrence or hyperopia computed tomography or magnetic resonance imaging. Patients without imaging were followed. RESULTS...... no obvious neurological signs at onset. Four significant risk factors for intracranial disease were identified as follows: larger esodeviation at distance, recurrence of AACE, neuro signs (papilledema) and older age at onset (>6 years). CONCLUSION: In a large case series of children with AACE and by review...... of literature, we identified seven cause-specific types of AACE. Intracranial disease was present in 6%, and four risk factors were identified to guide clinicians when to perform brain imaging. Findings suggest AACE of childhood to be differentiated from AACE of adulthood....

  3. Prognostic factors in children with acute lymphoblastic leukemia: a ten year study

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    Oloomi yazdi Z.

    2008-06-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common cancer in the pediatric population. With modern treatments, the chance of the complete recovery is nearly 100%. The most important prognostic factors are appropriate treatment protocol and determination of patient risk factors based on clinical, morphological, immunological and cytological characteristics. In this study we reviewed frequency of these factors, like as age, gender, the primary white blood cell number, sub- group on the base of FAB classification, immunophenotype and the clinical progress. Methods: In this retrospective study, we reviewed 877 pediatric patients with the diagnosis of ALL between the years of 1994 and 2004. In these patients the age, gender, primary WBC count, sub-group based on the FAB classification, immunophenotype and the clinical progress in 177 patient with acute lymphoblastic leukemia at Imam Khomeini Hospital between the years of 1994 to 2004 were determined. Results: Of these patients, 1.6% was younger than one year, 24.8% more than ten years old and 73.6% were between the ages of one and ten years; 63.8% were male. WBC counts were above 50,000/ul in 28.8% of the patients. FAB classifications included L1 in 80.2%, L2 in 17.5% and L3 in 2.3% of the patients. Immunophenotypes included pre-B cell in 63.8%, early pre-B cell in 23.1%, T cell in 12.3% and mature B cell in 0.8% of the patients. Marker CD10+ was detected in 88.1% of the B cell cases. In this study group, 74% of the patients recovered, 16.3% died and 16.5% relapsed.Conclusions: The prevalence of FAB-L1 and pre-B cell cases in this study is greater than a previous study, while the prevalence of FAB-L2 and early pre-B cell cases is less than that of the previous study.

  4. Genotyping NUDT15 can predict the dose reduction of 6-MP for children with acute lymphoblastic leukemia especially at a preschool age.

    Science.gov (United States)

    Suzuki, Hisato; Fukushima, Hiroko; Suzuki, Ryoko; Hosaka, Sho; Yamaki, Yuni; Kobayashi, Chie; Sakai, Aiko; Imagawa, Kazuo; Iwabuchi, Atsushi; Yoshimi, Ai; Nakao, Tomohei; Kato, Keisuke; Tsuchida, Masahiro; Kiyokawa, Nobutaka; Koike, Kazutoshi; Noguchi, Emiko; Fukushima, Takashi; Sumazaki, Ryo

    2016-09-01

    The pharmacokinetics among children has been altered dynamically. The difference between children and adults is caused by immaturity in things such as metabolic enzymes and transport proteins. The periods when these alterations happen vary from a few days to some years after birth. We hypothesized that the effect of gene polymorphisms associated with the dose of medicine could be influenced by age. In this study, we analyzed 51 patients with childhood acute lymphoblastic leukemia (ALL) retrospectively. We examined the associations between the polymorphism in NUDT15 and clinical data, especially the dose of 6-mercaptopurine (6-MP). Ten of the patients were heterozygous for the variant allele in NUDT15. In patients under 7 years old with NUDT15 variant allele, the average administered dose of 6-MP was lower than that for the patients homozygous for the wild-type allele (P=0.04). Genotyping of NUDT15 could be a beneficial to estimate the tolerated dose of 6-MP for patients with childhood ALL, especially at a preschool age in Japan. Furthermore, the analysis with stratification by age might be useful in pharmacogenomics among children.

  5. Progress of Studies on Genetics of Childhood Acute Leukemia——Review%儿童急性白血病遗传学研究进展

    Institute of Scientific and Technical Information of China (English)

    岳志霞; 郑胡镛

    2013-01-01

    This study on determination of leukemia-specific chromosomal abnormalities and their relationship with prognosis of childhood acute leukemia(AL) had an important significance for childhood acute leukemia.In recent years,the efficacy of treatment of childhood AL has been greatly improved,but relapse is still a main factor affecting prognosis.Treatment based on the risk stratification by cytogenetic abnormalities can improve the prognosis and survival rate.In the past 3 decades,the genetic techniques have developed rapidly and many new genetic abnormalities have been found.This review highlights the main chromosomal and genomic abnormalities of 3 common childhood AL,including B-cell precursor acute lymphoblastic leukemia(BCP-ALL),T-cell acute lymphoblastic leukemia(T-ALL) and acute myeloid leukemia(AML).%白血病特异染色体异常的确定及其与预后关系的研究对儿童急性白血病(acute leukemia,AL)具有极其重要的意义.近年来,虽然儿童AL的治疗效果有了很大改善,但其复发仍然是影响预后的主要因素.根据遗传学异常进行危险度分层,并指导治疗,可以改善儿童AL预后,提高患儿生存率.在过去的30年中,遗传学检测技术有了突飞猛进的发展,发现了许多新的遗传学异常.本文就三种儿童常见AL,包括前B细胞急性淋巴细胞白血病(B-cell precursor acute lymphoblastic leukemia,BCP-ALL)、T细胞急性淋巴细胞白血病(T-cell acute lymphoblastic leukemia,T-ALL)和急性髓系白血病(acute myeloid leukemia,AML)的最新遗传学研究进展进行综述.

  6. Obesity as the initial manifestation of central nervous system relapse of acute lymphoblastic leukemia: case report and literature review.

    Science.gov (United States)

    Zhang, Li-Dan; Li, Yan-Hong; Ke, Zhi-Yong; Huang, Li-Bin; Luo, Xue-Qun

    2012-01-01

    A 6-year-old boy with acute lymphoblastic leukemia in remission experienced hyperphagia, obesity, and emotional disorders. Cytomorphologic examination of cerebral spinal fluid (CSF) and cranial MRI did not help in differentiating between central nervous system leukemia (CNSL) and other CNS diseases including tuberculosis in this boy. Flow cytometric CSF analysis on repeated lumber puncture detected lymphoblasts, while microscopic CSF examination did not definitively show relapse disease. The diagnosis of CNSL was thus made and confirmed by the response to leukemia treatment. Obesity can be the first manifestation of CNSL and the diagnosis can be challenging. A combination of CSF cytomorphology, CSF flow cytometry, and cranial MRI can be useful in the diagnosis of the disease. Two mechanisms of CNSL-related obesity are discussed based on the literature review.

  7. Effect of Malnutrition at Diagnosis on Clinical Outcomes of Children With Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Yazbeck, Nadine; Samia, Loma; Saab, Raya; Abboud, Miguel R; Solh, Hassan; Muwakkit, Samar

    2016-03-01

    Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. Although studies have shown that malnutrition can negatively affect treatment outcome, results are controversial. This retrospective study aims at determining the prevalence of malnutrition and its association with treatment outcome among children with ALL treated at the Children's Cancer Institute in Lebanon. A total of 103 patients diagnosed with ALL between April 2002 and May 2010 were enrolled. Anthropometric data were collected from medical records upon diagnosis, at 3 and 6 months, and at the end of treatment. Body mass index was calculated for children 2 years of age and older, whereas weight-for-height ratio was used for patients below 2 years. Patients were considered underweight, stunted, or wasted if their Z-scores were <-2 SD. The prevalence of malnourished children was 25.2% at diagnosis and remained almost the same at the end of treatment. The odds of having a poor outcome (death and relapse) was higher among malnourished children and more so among stunted children with an odds ratios=2.15; 95% confidence interval, 0.5-8.3 and odds ratio=2.63; 95% confidence interval, 0.6-11.5, respectively. Although there was a trend showing worse outcomes in malnourished children with ALL at diagnosis when compared with well-nourished children larger studies using additional tools like arm anthropometry need to be conducted to prove the association.

  8. The Study on BCR/ABL Fusion Gene in Adult Acute Lymphoblastic Leukemia

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In order to assess the significance of BCR/ABC fusion gene in adult acute lymphoblastic Leukemia (ALL), 28 patients who were diagnosed as ALL were enrolled to detect BCR/ABC gene using nested-RT PCR. The results showed that 9 cases (31.25%) were BCR/ABL positive ,and expressed P210 subtype. A mong them 7 cases were B-ALL, and one was T-ALL. The diagnosis was proved by monoclonal antibodies recognition by indirect immunofluorescence. Adult patients with BCR/ABL positive ALL were significantly older (p<0. 01) and had higher WBC count (p<0. 01) as compared with BCR/ABL-negative patients. There was no significant difference in sex, hemoglobin and splenomegaly between two group (p>0. 05). The induc tion failure rate was high in BCR/ABL positive patients and those who achieved complete remission usually relapsed earlier. In conclusion, adult ALL patients with BCR/ABL-positive have poorer prognosis.

  9. The risk factors for thrombosis in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Sivaslioglu, Selda; Gursel, Turkiz; Kocak, Ulker; Kaya, Zuhre

    2014-09-01

    We aimed to scrutinize the risk factors for thrombosis in children with acute lymphoblastic leukemia treated with the Berlin-Frankfurt-Münster 95 protocol. The study population was 82 children younger than 16 years of age. The children were followed up for 10 years until January 2007. Thrombosis occurred in 10 (12%) of 82 patients during the treatment course, mainly after the M protocol. The most common risk factor was factor V Leiden (FVL; 15.6%). This was followed by methyleneterahydrofolate reductase (MTHFR; 9.3%), elevated lipoprotein (1.5%), and prothrombin (PT) 20210A (1.5%) in descending order. The risk of thrombosis was found to be significantly high in patients with FVL mutation (odds ratio = 7.1, 95% confidence interval = 1.6-30.5). The risk of thrombosis was not significant in patients with MTHFR and PT20210A mutation (P = .2). Age, catheter usage, FVL mutation, and prednisolone treatment are significant risk factors for thromboemboli occurrence.

  10. Age and leukocyte count as prognostic factors on acute lymphoblastic leukemia: hgmlal07 cohort

    Directory of Open Access Journals (Sweden)

    Washington Ladines-Castro

    2016-07-01

    Full Text Available In order to establish the cutoff with prognostic implications for white blood cell count and age at diagnosis in adults with acute lymphoblastic leukemia (ALL, we conducted an observational, descriptive and analytical study nested in a retrospective cohort of patients with ALL treated by institutional protocol HGMLAL07 during 2007-2014. We study 255 patients, the 52.9% (n=135 were female and 47.1% (n=120 were male. The mean age was 31 (16-80 years-old. The disease-free survival (DFS decreases in both genders after 20 years-old (p = 0.001. Leukocyte count average was 56.1 x 109/L (0.1-850 x 109/L. DFS decreases significantly from an equal or greater leukocyte count of 20 x 109/L (p<0.05. With this results, we can conclude that use foreign cutoff for age and leukocyte count could determine a bad prognosis stratification and a consequent suboptimal treatment.

  11. Isolated testicular relapse in acute lymphoblastic leukemia - Effective treatment with the modified CCG-112 protocol

    Directory of Open Access Journals (Sweden)

    Shama Goyal

    2005-01-01

    Full Text Available BACKGROUND: The testes have been considered a sanctuary site for leukemic cells and testicular relapses used to account for a major proportion of the poor outcome of boys with acute lymphoblastic leukemia. With use of aggressive chemotherapy which includes intermediate or high dose methotrexate, the incidence of testicular relapses has declined. However once these patients have received cranial irradiation as a part of the front line protocol, high dose methotrexate needs to be avoided because of risk of developing leucoencephalopathy. AIM: To study the use of non cross resistant chemotherapeutic agents along with a regimen containing lower doses of methotrexate in patients of isolated testicular relapse (ITR. MATERIALS AND METHODS: This is a retrospective analysis of 12 consecutive patients with ITR treated with modified version of the CCG-112 protocol which consists of intensive systemic chemotherapy, cranial chemoprophylaxis along with testicular irradiation. RESULTS: One patient died of regimen related toxicity. Two patients relapsed in the bone marrow during maintenance. Of the nine patients who completed treatment, eight are alive and in remission. One patient had a bone marrow relapse two months after completing treatment. The Kaplan Meier estimates give us an Event Free Survival (EFS of 66.7% at 10 yrs. CONCLUSIONS: Thus, though the incidence is very low, patients with ITR should be treated aggressively since they have an excellent chance of achieving a long term EFS.

  12. Acute lymphoblastic leukemia masquerading as juvenile rheumatoid arthritis: diagnostic pitfall and association with survival.

    Science.gov (United States)

    Marwaha, Ram Kumar; Kulkarni, Ketan Prasad; Bansal, Deepak; Trehan, Amita

    2010-03-01

    Acute lymphoblastic leukemia (ALL) often presents with osteoarthritic manifestations which may lead to misdiagnosis with juvenile rheumatoid arthritis (JRA). This study was designed to identify ALL patients with initial diagnosis of JRA, compare their clinicolaboratory characteristics and outcome with other ALL patients treated at our center. Case records of 762 patients with ALL were analyzed. Information regarding the clinical-demographic profile, therapy and outcome were recorded. Of the children, 49 (6.4%) had initial presentation mimicking JRA. Asymmetric oligoarthritis was the most common pattern of joint involvement. Majority presented with fever, pallor, arthritis, night pain, and bone pain. None of the routine prognostic factors including age, gender, lymphadenopathy, hepatosplenomegaly, total leukocytes count (TLC), and platelet count were significantly associated with relapse/death. The mean symptom-presentation interval (SPI), hemoglobin was significantly higher whilst the TLC was significantly lower in these patients compared to other ALL patients. The 5 year overall-survival was better than other patients with ALL (p = 0.06, by logrank test). Significantly longer SPI in these patients underscores the need for prompt and early investigations to rule out ALL in patients of JRA with atypical features and pointers of ALL. Children with ALL-mimicking JRA may belong to a subgroup of ALL with a better prognosis.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    (MLL-R cases) with leukemia. Our data show that infant MLL-R ALL has one of the lowest frequencies of somatic mutations of any sequenced cancer, with the predominant leukemic clone carrying a mean of 1.3 non-silent mutations. Despite this paucity of mutations, we detected activating mutations in kinase......Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older children......-PI3K-RAS signaling pathway components in 47% of cases. Surprisingly, these mutations were often subclonal and were frequently lost at relapse. In contrast to infant cases, MLL-R leukemia in older children had more somatic mutations (mean of 6.5 mutations/case versus 1.3 mutations/case, P = 7.15 × 10...

  14. Challenges faced in the treatment of acute lymphoblastic leukemia in adolescents and young adults

    Directory of Open Access Journals (Sweden)

    Levine SR

    2016-02-01

    Full Text Available Selena R Levine,1 Jennifer L McNeer,2 Michael S Isakoff1 1Center for Cancer and Blood Disorders, Connecticut Children’s Medical Center and University of Connecticut School of Medicine, Hartford, CT, 2Section of Pediatric Hematology/Oncology, University of Chicago Comer Children's Hospital, Chicago, IL, USA Abstract: The survival rate for children with acute lymphoblastic leukemia (ALL has dramatically improved over the last 50 years. However, for those in the adolescent and young adult (AYA age-group of 15–30 years with ALL, there has not been the same degree of improvement. Historically, pediatric and adult providers have utilized different treatment approaches based on clinical trials. However, studies that have compared the outcome of AYA patients with ALL treated on pediatric or adult clinical trials have generally shown substantially better outcomes for this patient population treated with the pediatric trials. Additionally, hematopoietic stem cell transplantation has been considered as part of intensified therapy for AYA patients with ALL. Herein, we review the outcomes with chemotherapy alone and with hematopoietic stem cell transplantation, and explore the challenges faced in determining the ideal therapy for the AYA population of patients. Keywords: adolescent young adult oncology, leukemia, hematopoietic stem cell transplantation

  15. Acute lymphoblastic leukaemia: cyclical chemotherapy with three combinations of four drugs (COAP-POMP-CART regimen).

    Science.gov (United States)

    Spiers, A S; Roberts, P D; Marsh, G W; Parekh, S J; Franklin, A J; Galton, D A; Szur, Z L; Paul, E A; Husband, P; Wiltshaw, E

    1975-12-13

    Forty-two adults and children with previously untreated acute lymphoblastic leukaemia (ALL) were entered into a programme of chemotherapy in which three combinations, each of four drugs were administered in a predetermined cyclical rotation together with cranial irradiation and intrathecal injections of methotrexate. Forty-one patients (98%) entered remission and no patient developed neuroleukaemia. Relapse of ALL occurred in 10 patients, and three patients died during remission, while eight patients stopped treatment after two and a half years and have remained in remission for two to 26 months. Comparison of remission and survival experience in this mixed group of children and adults with the experience of children treated at Memphis and in the Medical Research Council's UKALL-I trial showed no significant differences. On the other hand, analysis by prognostic factors showed that neither age nor blast cell count at presentation had any adverse effect in patients treated in this study. No relapses occurred in nine patients with blast cell counts greater than 20 x 109/1 at presentation. This regimen is effective treatment for ALL and may be of special value in patients with poor prognoses. The regiment has not as yet proved superior for the treatment of children with ALL who do not have adverse prognostic features.

  16. Modeling the Mechanism of GR/c-Jun/Erg Crosstalk in Apoptosis of Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Chen, Daphne Wei-Chen; Krstic-Demonacos, Marija; Schwartz, Jean-Marc

    2012-01-01

    Acute lymphoblastic leukemia (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 adopting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data by building a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Ets-related gene (Erg) as potential biomarker of GC resistance. The results revealed an alternative possible 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.

  17. Atypical Structural Connectome Organization and Cognitive Impairment in Young Survivors of Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Kesler, Shelli R; Gugel, Meike; Huston-Warren, Emily; Watson, Christa

    2016-05-01

    Survivors of pediatric acute lymphoblastic leukemia (ALL) are at increased risk for cognitive impairments that disrupt everyday functioning and decrease quality of life. The specific biological mechanisms underlying cognitive impairment following ALL remain largely unclear, but previous studies consistently demonstrate significant white matter pathology. We aimed to extend this literature by examining the organization of the white matter connectome in young patients with a history of ALL treated with chemotherapy only. We applied graph theoretical analysis to diffusion tensor imaging obtained from 31 survivors of ALL age 5-19 years and 39 matched healthy controls. Results indicated significantly lower small-worldness (p = 0.007) and network clustering coefficient (p = 0.019), as well as greater cognitive impairment (p = 0.027) in the ALL group. Regional analysis indicated that clustered connectivity in parietal, frontal, hippocampal, amygdalar, thalamic, and occipital regions was altered in the ALL group. Random forest analysis revealed a model of connectome and demographic variables that could automatically classify survivors of ALL as having cognitive impairment or not (accuracy = 0.89, p regional connectivity.

  18. Characterization of Pediatric Acute Lymphoblastic Leukemia Survival Patterns by Age at Diagnosis

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    Md Jobayer Hossain

    2014-01-01

    Full Text Available Age at diagnosis is a key prognostic factor in pediatric acute lymphoblastic leukemia (ALL survivorship. However, literature providing adequate assessment of the survival variability by age at diagnosis is scarce. The aim of this study is to assess the impact of this prognostic factor in pediatric ALL survival. We estimated incidence rate of mortality, 5-year survival rate, Kaplan-Meier survival function, and hazard ratio using the Surveillance Epidemiology and End Results (SEER data during 1973–2009. There was significant variability in pediatric ALL survival by age at diagnosis. Survival peaked among children diagnosed at 1–4 years and steadily declined among those diagnosed at older ages. Infants (<1 year had the lowest survivorship. In a multivariable Cox proportional hazard model stratified by year of diagnosis, those diagnosed in age groups 1–4, 5–9, 10–14, and 15–19 years were 82%, 75%, 57%, and 32% less likely to die compared to children diagnosed in infancy, respectively. Age at diagnosis remained to be a crucial determinant of the survival variability of pediatric ALL patients, after adjusting for sex, race, radiation therapy, primary tumor sites, immunophenotype, and year of diagnosis. Further research is warranted to disentangle the effects of age-dependent biological and environmental processes on this association.

  19. Acute lymphoblastic leukemia in adolescents and young adults – from genomics to the clinics

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    Kenderian SS

    2013-04-01

    Full Text Available Saad Sirop Kenderian, Mark R Litzow Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA Abstract: Acute lymphoblastic leukemia (ALL in adolescents and young adults (AYA represents a unique and challenging disease entity. Despite the recent improvement of survival in this population over the last decade, it is still lagging behind the excellent cure rates obtained in pediatric ALL. This special population of AYA receives care from pediatric as well as adult hematologists and can be treated on pediatric or adult protocols. There is a substantial difference in disease biology, response to chemotherapy, and allogeneic stem cell transplantation between pediatric and AYA patients. This review discusses current controversies in the management of AYA, outcomes following treatment with pediatric and adult protocols, and the role of allogeneic stem cell transplantation. It focuses on the unique clinical, biological, and socioeconomic characteristics of this population that might partly explain the inferior outcomes. This review also explores recent advances in genomic profiling and emerging treatments in ALL. Keywords: novel agents, monoclonal antibodies, stem cell transplantation, bone marrow transplantation, Philadelphia positive ALL, genomic profile

  20. Novel dynamin 2 mutations in adult T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    Ge, Zheng; Li, Min; Zhao, Gang; Xiao, Lichan; Gu, Yan; Zhou, Xilian; Yu, Michael D.; Li, Jianyong; Dovat, Sinisa; Song, Chunhua

    2016-01-01

    Genetic mutations on signaling pathways are found in patients with T-cell acute lymphoblastic leukemia (T-ALL) and act as markers of high-risk leukemia. Mutations in dynamin 2 (DNM2) have been reported in T-ALL, particularly in early T-cell precursor-ALL. In the present study, DNM2 mutations were screened by sequencing DNM2 exons obtained by polymerase chain reaction amplification and gel purification in adult T-ALL patients. A total of 4 novel DNM2 mutations were identified in adult T-ALL patients, with a mutation rate of 9.5%, and the DNM2 mutations were found to co-exist with NOTCH1 and PHD finger protein 6, and were also associated with high-risk leukemia. A high rate of silent mutation was also found in the patients, but no significant association was found between the silent mutations and patients' clinical features. The present findings suggested the DNM2 mutations may be involved in the oncogenesis of T-ALL.

  1. Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia

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    Yuan-Fang Liu

    2016-06-01

    Full Text Available Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL were investigated using next-generation sequencing and copy number alteration analysis. Recurrent gene mutations and fusions were tested in an additional 87 adult and 93 pediatric patients. Among the 29 newly identified in-frame gene fusions, those involving MEF2D and ZNF384 were clinically relevant and were demonstrated to perturb B-cell differentiation, with EP300-ZNF384 inducing leukemia in mice. Eight gene expression subgroups associated with characteristic genetic abnormalities were identified, including leukemia with MEF2D and ZNF384 fusions in two distinct clusters. In subgroup G4 which was characterized by ERG deletion, DUX4-IGH fusion was detected in most cases. This comprehensive dataset allowed us to compare the features of molecular pathogenesis between adult and pediatric B-ALL and to identify signatures possibly related to the inferior outcome of adults to that of children. We found that, besides the known discrepancies in frequencies of prognostic markers, adult patients had more cooperative mutations and greater enrichment for alterations of epigenetic modifiers and genes linked to B-cell development, suggesting difference in the target cells of transformation between adult and pediatric patients and may explain in part the disparity in their responses to treatment.

  2. Hypothalamus-pituitary-adrenal axis suppression following induction chemotherapy in children with acute lymphoblastic leukemia

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    Perdomo-Ramírez, Iván

    2016-01-01

    Full Text Available Background: Adrenal insufficiency has been reported in 46 % to 81.5 % of children receiving corticosteroids for acute lymphoblastic leukemia (ALL. Methodology: To assess the frequency of such insufficiency, 40 patients under 18 years (mean: 8.5 years with new diagnosis of ALL were studied. Base-line cortisol and adrenocorticotropin (ACTH levels were measured, and they received 5-week therapy with prednisolone. After 3 days off-steroid therapy, a stimulation test with ACTH 1 μg was done. In patients with abnormal cortisol (<18 μg/dL new ACTH tests were done and cortisol levels were determined at days 7, 14 and 30 until cortisol post-stimulation levels were normal. Results: Three days after the last steroid dose 29/40 (72.5 % had adrenal insufficiency after ACTH stimulus. At day 30 no one had abnormal cortisol levels after ACTH stimulus. All patients with adrenal suppression were over 5 years (HR 4.69; CI95 %: 1.44-15.32; p = 0.011. Conclusion: Steroids used during ALL treatment may cause adrenal insufficiency. Patients over 5 years are at high risk of developing adrenal suppression. We suggest to follow-up those patients with stress episodes after induction chemotherapy as steroid supplementation may be indicated.

  3. UTX inhibition as selective epigenetic therapy against TAL1-driven T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    Benyoucef, Aissa; Palii, Carmen G.; Wang, Chaochen; Porter, Christopher J.; Chu, Alphonse; Dai, Fengtao; Tremblay, Véronique; Rakopoulos, Patricia; Singh, Kulwant; Huang, Suming; Pflumio, Francoise; Hébert, Josée; Couture, Jean-Francois; Perkins, Theodore J.; Ge, Kai; Dilworth, F. Jeffrey; Brand, Marjorie

    2016-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous group of hematological tumors composed of distinct subtypes that vary in their genetic abnormalities, gene expression signatures, and prognoses. However, it remains unclear whether T-ALL subtypes differ at the functional level, and, as such, T-ALL treatments are uniformly applied across subtypes, leading to variable responses between patients. Here we reveal the existence of a subtype-specific epigenetic vulnerability in T-ALL by which a particular subgroup of T-ALL characterized by expression of the oncogenic transcription factor TAL1 is uniquely sensitive to variations in the dosage and activity of the histone 3 Lys27 (H3K27) demethylase UTX/KDM6A. Specifically, we identify UTX as a coactivator of TAL1 and show that it acts as a major regulator of the TAL1 leukemic gene expression program. Furthermore, we demonstrate that UTX, previously described as a tumor suppressor in T-ALL, is in fact a pro-oncogenic cofactor essential for leukemia maintenance in TAL1-positive (but not TAL1-negative) T-ALL. Exploiting this subtype-specific epigenetic vulnerability, we propose a novel therapeutic approach based on UTX inhibition through in vivo administration of an H3K27 demethylase inhibitor that efficiently kills TAL1-positive primary human leukemia. These findings provide the first opportunity to develop personalized epigenetic therapy for T-ALL patients. PMID:26944678

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

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    Youssef Al-Tonbary

    2009-01-01

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

  5. Whole brain magnetization transfer histogram analysis of pediatric acute lymphoblastic leukemia patients receiving intrathecal methotrexate therapy

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    Yamamoto, Akira [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: yakira@kuhp.kyoto-u.ac.jp; Miki, Yukio [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: mikiy@kuhp.kyoto-u.ac.jp; Adachi, Souichi [Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: sadachi@kuhp.kyoto-u.ac.jp (and others)

    2006-03-15

    Background and purpose: The purpose of this prospective study was to evaluate the hypothesis that magnetization transfer ratio (MTR) histogram analysis of the whole brain could detect early and subtle brain changes nonapparent on conventional magnetic resonance imaging (MRI) in children with acute lymphoblastic leukemia (ALL) receiving methotrexate (MTX) therapy. Materials and methods: Subjects in this prospective study comprised 10 children with ALL (mean age, 6 years; range, 0-16 years). In addition to conventional MRI, magnetization transfer images were obtained before and after intrathecal and intravenous MTX therapy. MTR values were calculated and plotted as a histogram, and peak height and location were calculated. Differences in peak height and location between pre- and post-MTX therapy scans were statistically analyzed. Conventional MRI was evaluated for abnormal signal area in white matter. Results: MTR peak height was significantly lower on post-MTX therapy scans than on pre-MTX therapy scans (p = 0.002). No significant differences in peak location were identified between pre- and post-chemotherapy imaging. No abnormal signals were noted in white matter on either pre- or post-MTX therapy conventional MRI. Conclusions: This study demonstrates that MTR histogram analysis allows better detection of early and subtle brain changes in ALL patients who receive MTX therapy than conventional MRI.

  6. Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia

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    Idalia Garza-Veloz

    2015-01-01

    Full Text Available Background. Acute lymphoblastic leukemia type B (B-ALL is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL. Methods. 219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by quantitative real-time polymerase chain reaction. Results. Normalized delta Cq values of 23 genes showed differences between B-ALL and controls at diagnosis time (P values < 0.05. There were significant associations between B-ALL patients relapse/death and the expression levels of IL2RA, SORT1, DEFA1, and FLT3 genes at least in one of the times evaluated (P values < 0.05 and odds ratio ranges: 3.73–27. The association between FLT3 deregulation and relapse/death was a constant in the times studied and their overexpression significantly increased the odds of relapse/death in a range of 3.73 and 6.05 among study population (P values < 0.05. Conclusions. Overexpression of FLT3 and DEFA1 genes retained independent prognostic significance for B-ALL outcome, reflected as increased risks of relapse/death among the study population.

  7. Effects of insulin-like growth factor-1 on B-cell precursor acute lymphoblastic leukemia.

    Science.gov (United States)

    Yamada, Hiroyuki; Iijima, Kazutoshi; Tomita, Osamu; Taguchi, Tomoko; Miharu, Masashi; Kobayashi, Kenichiro; Okita, Hajime; Saito, Masahiro; Shimizu, Toshiaki; Kiyokawa, Nobutaka

    2013-01-01

    Insulin-like growth factor-1 (IGF-1) is known to be a major growth factor with effects on various cell types, including hematopoietic cells, as well as neoplasms, and is regulated by IGF-binding proteins (IGFBPs). In this study, we investigated the effects of IGF-1 on B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. When the expression of IGF-1R in clinical samples of BCP-ALL was examined, five of thirty-two cases showed IGF-1R expression, whereas IGF-1R was expressed in most BCP-ALL cell lines. We observed that IGF-1 enhanced the proliferation of BCP-ALL cell lines that can be partially inhibited by IGFBP-1, -3, and -4, but not other IGFBPs. IGF-1 also partially inhibited dexamethasone-induced apoptosis, but not apoptosis mediated by VP-16 and irradiation. Interestingly, the proliferative effect of IGF-1 was partially blocked by inhibitors of MAPK and AKT, whereas the inhibition of dexamethasone-induced apoptosis was completely blocked by both inhibitors. Our data indicate that IGF-1 is involved in cell proliferation and apoptosis regulation in BCP-ALL cells. Since some BCP-ALL cases express IGF-1R, it appears to be a plausible target for prognostic evaluation and may represent a new therapeutic strategy.

  8. Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Jaime-Perez, Jose Carlos; Carrillo-Sanchez, Karol; Ramos-Del Hoyo, Maria Guadalupe; Lugo-Trampe, Angel; Gutierrez-Aguirre, Cesar Homero; Gonzalez-Llano, Oscar; Salazar-Riojas, Rosario; Hidalgo-Miranda, Alfredo; Gomez-Almaguer, David

    2015-01-01

    Background. Acute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL. Methods. 219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by quantitative real-time polymerase chain reaction. Results. Normalized delta Cq values of 23 genes showed differences between B-ALL and controls at diagnosis time (P values < 0.05). There were significant associations between B-ALL patients relapse/death and the expression levels of IL2RA, SORT1, DEFA1, and FLT3 genes at least in one of the times evaluated (P values < 0.05 and odds ratio ranges: 3.73–27). The association between FLT3 deregulation and relapse/death was a constant in the times studied and their overexpression significantly increased the odds of relapse/death in a range of 3.73 and 6.05 among study population (P values < 0.05). Conclusions. Overexpression of FLT3 and DEFA1 genes retained independent prognostic significance for B-ALL outcome, reflected as increased risks of relapse/death among the study population. PMID:25802479

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

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    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.

  10. Dengue fever causing febrile neutropenia in children with acute lymphoblastic leukemia: an unknown entity.

    Science.gov (United States)

    Ramzan, Mohammed; Yadav, Satya Prakash; Dinand, Veronique; Sachdeva, Anupam

    2013-06-01

    Dengue fever is endemic in many parts of the world but it has not been described as a cause of febrile neutropenia. We describe here clinical features, laboratory values and outcome in 10 children with acute lymphoblastic leukemia (ALL) and with dengue fever as a cause of febrile neutropenia. These data are compared to an age-matched control population of 22 children with proven dengue infection without ALL. Except for fever in all patients and plethoric face in one patient, typical symptoms of dengue such as abdominal pain, myalgias, and headaches, were absent. Mean duration of hospital stay was 6.3±2.0 days in ALL patients vs. 5.0±2.0 in controls (p=0.096). Median platelet count was 13,000/cmm (range 1000-28,000) in cases vs. 31,500 (range 13,000-150,000) in controls (p=0.018). Mean time for recovery for platelet was 6.0±1.3days in ALL patients vs. 2.5±0.9days in controls (pfebrile neutropenia although typical symptoms may be lacking. Platelet recovery may be significantly delayed.

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

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    Ji Fuyun

    2011-10-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA alterations, including mtDNA copy number and mtDNA 4977 bp common deletion (CD, are key indicators of irradiation-induced damage. The relationship between total body irradiation (TBI treatment and mtDNA alterations in vivo, however, has not been postulated yet. The aim of this study is to analyze mtDNA alterations in irradiated human peripheral lymphocytes from acute lymphoblastic leukemia (ALL patients as well as to take them as predictors for radiation toxicity. Methods Peripheral blood lymphocytes were isolated from 26 ALL patients 24 hours after TBI preconditioning (4.5 and 9 Gy, respectively. Extracted DNA was analyzed by real-time PCR method. Results Average 2.31 times mtDNA and 0.53 fold CD levels were observed after 4.5 Gy exposure compared to their basal levels. 9 Gy TBI produced a greater response of both mtDNA and CD levels than 4.5 Gy. Significant inverse correlation was found between mtDNA content and CD level at 4.5 and 9 Gy (P = 0.037 and 0.048. Moreover, mtDNA content of lymphocytes without irradiation was found to be correlated to age. Conclusions mtDNA and CD content may be considered as predictive factors to radiation toxicity.

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

    Science.gov (United States)

    von Bergh, Anne R M; Beverloo, H Berna; Rombout, Paul; van Wering, Elisabeth R; van Weel, Margreet H; Beverstock, Geoffrey C; Kluin, Philip M; Slater, Rosalyn M; Schuuring, Ed

    2002-09-01

    Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is characterized by a proB phenotype and a poor clinical outcome. We analyzed an infant proB ALL with t(2;11)(p15;p14) and an MLL rearrangement on Southern blot analysis. Rapid amplification of cDNA ends-polymerase chain reaction (PCR) and reverse transcriptase-PCR identified the LAF4 gene mapped on chromosome region 2q11.2-q12 as a fusion partner of the MLL gene. The LAF4 gene was identified previously by its high sequence homology to the AF4 protein and encodes a protein of 1,227 amino acids. The t(4;11)(q21;q23), creating the MLL-AF4 chimeric transcripts, is the predominant 11q23 chromosome translocation in infant ALL and is associated with an extremely poor prognosis. Our findings further suggest that fusion of MLL to one of the AF4 family members (AF4/LAF4/AF5Q31) might determine a proB-cell phenotype in infant leukemia.

  13. CENTRAL NERVOUS SYSTEM INVOLVEMENT IN ADULT ACUTE LYMPHOBLASTIC LEUKEMIA: DIAGNOSTIC TOOLS, PROPHYLAXIS AND THERAPY

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    Maria Ilaria Del Principe

    2014-11-01

    Full Text Available In adult patients with acute lymphoblastic leukemia (ALL, Central Nervous System (CNS involvement is associated with a very poor prognosis. The diagnostic assessment of this condition relies on the use of neuroradiology, conventional cytology (CC and flow cytometry (FCM. Among these approaches, which is the gold standard it is still a matter of debate. Neuroradiology and CC have a limited sensitivity with a higher rate of false negative results. FCM demonstrated a superior sensitivity over CC, particularly when low levels of CNS infiltrating cells are present. Although prospective studies of large series of patients are still awaited, a positive finding by FCM appears to anticipate an adverse outcome even if CC shows no infiltration. Current strategies for adult ALL CNS-directed prophylaxis or therapy involve systemic and intrathecal chemotherapy and radiation therapy. Actually, early and frequent intrathecal injection of cytostatic combined with systemic chemotherapy is the most effective strategy to reduce the frequency of CNS involvement. In patients with CNS overt ALL, at diagnosis or upon relapse, allogenic hematopoietic stem cell transplantation might be considered. This review will discuss risk factors, diagnostic techniques for identification of CNS infiltration and modalities of prophylaxis and therapy to manage it.

  14. Skeletal, neuromuscular and fitness impairments among children with newly diagnosed acute lymphoblastic leukemia

    Science.gov (United States)

    Ness, Kirsten K.; Kaste, Sue C.; Zhu, Liang; Pui, Ching-Hon; Jeha, Sima; Nathan, Paul C.; Inaba, Hiroto; Wasilewski-Masker, Karen; Shah, Durga; Wells, Robert J.; Karlage, Robyn E.; Robison, Leslie L.; Cox, Cheryl L.

    2014-01-01

    This study describes skeletal, neuromuscular and fitness impairments among 109 children (median age 10 (range 4–18) years, 65.1% male, 63.3% white) with acute lymphoblastic leukemia (ALL), enrolled on a physical activity trial from 2009 to 2013. Outcomes were measured 7-10 days after diagnosis and compared to age- and sex-specific expected values. Associations between function and HRQL were evaluated with logistic regression. Children low values for BMD z-scores/height (mean±standard error: −0.53±0.16 vs. 0.00±0.14, p <0.01), body mass index percentile (57.6±3.15 vs. 50.0±3.27%, p=0.02), quadriceps strength (201.9±8.3 vs. 236.1±5.4 Newtons, p<0.01), six minute walk distance (385.0±13.1 vs. 628.2±7.1 meters, p < 0.001), and Bruininks-Oseretsky Test of Motor Proficiency (23±2.5 vs. 50±3.4%, p < 0.001). Quadriceps weakness was associated with a 20.9-fold (95% CI 2.5–173.3) increase in poor physical HRQL. Children with newly diagnosed ALL have weakness and poor endurance and may benefit from early rehabilitation that includes strengthening and aerobic conditioning. PMID:25030039

  15. Microarray-based genomic profiling as a diagnostic tool in acute lymphoblastic leukemia.

    Science.gov (United States)

    Simons, Annet; Stevens-Kroef, Marian; El Idrissi-Zaynoun, Najat; van Gessel, Sabine; Weghuis, Daniel Olde; van den Berg, Eva; Waanders, Esmé; Hoogerbrugge, Peter; Kuiper, Roland; van Kessel, Ad Geurts

    2011-12-01

    In acute lymphoblastic leukemia (ALL) specific genomic abnormalities provide important clinical information. In most routine clinical diagnostic laboratories conventional karyotyping, in conjunction with targeted screens using e.g., fluorescence in situ hybridization (FISH), is currently considered as the gold standard to detect such aberrations. Conventional karyotyping, however, is limited in its resolution and yield, thus hampering the genetic diagnosis of ALL. We explored whether microarray-based genomic profiling would be feasible as an alternative strategy in a routine clinical diagnostic setting. To this end, we compared conventional karyotypes with microarray-deduced copy number aberration (CNA) karyotypes in 60 ALL cases. Microarray-based genomic profiling resulted in a CNA detection rate of 90%, whereas for conventional karyotyping this was 61%. In addition, many small (< 5 Mb) genetic lesions were encountered, frequently harboring clinically relevant ALL-related genes such as CDKN2A/B, ETV6, PAX5, and IKZF1. From our data we conclude that microarray-based genomic profiling serves as a robust tool in the genetic diagnosis of ALL, outreaching conventional karyotyping in CNA detection both in terms of sensitivity and specificity. We also propose a practical workflow for a comprehensive and objective interpretation of CNAs obtained through microarray-based genomic profiling, thereby facilitating its application in a routine clinical diagnostic setting.

  16. Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia

    Science.gov (United States)

    Gu, Zhaohui; Churchman, Michelle; Roberts, Kathryn; Li, Yongjin; Liu, Yu; Harvey, Richard C.; McCastlain, Kelly; Reshmi, Shalini C.; Payne-Turner, Debbie; Iacobucci, Ilaria; Shao, Ying; Chen, I-Ming; Valentine, Marcus; Pei, Deqing; Mungall, Karen L.; Mungall, Andrew J.; Ma, Yussanne; Moore, Richard; Marra, Marco; Stonerock, Eileen; Gastier-Foster, Julie M.; Devidas, Meenakshi; Dai, Yunfeng; Wood, Brent; Borowitz, Michael; Larsen, Eric E.; Maloney, Kelly; Mattano Jr, Leonard A.; Angiolillo, Anne; Salzer, Wanda L.; Burke, Michael J.; Gianni, Francesca; Spinelli, Orietta; Radich, Jerald P.; Minden, Mark D.; Moorman, Anthony V.; Patel, Bella; Fielding, Adele K.; Rowe, Jacob M.; Luger, Selina M.; Bhatia, Ravi; Aldoss, Ibrahim; Forman, Stephen J.; Kohlschmidt, Jessica; Mrózek, Krzysztof; Marcucci, Guido; Bloomfield, Clara D.; Stock, Wendy; Kornblau, Steven; Kantarjian, Hagop M.; Konopleva, Marina; Paietta, Elisabeth; Willman, Cheryl L.; L. Loh, Mignon; P. Hunger, Stephen; Mullighan, Charles G.

    2016-01-01

    Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered. PMID:27824051

  17. Childhood central nervous system leukemia: historical perspectives, current therapy, and acute neurological sequelae

    Energy Technology Data Exchange (ETDEWEB)

    Laningham, Fred H. [St. Jude Children' s Research Hospital, Division of Diagnostic Imaging, Department of Radiological Sciences, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States); Kun, Larry E. [St. Jude Children' s Research Hospital, Division of Radiation Oncology, Department of Radiological Sciences, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States); Reddick, Wilburn E.; Ogg, Robert J. [St. Jude Children' s Research Hospital, Division of Translational Imaging Research, Department of Radiological Sciences, Memphis, TN (United States); Morris, E.B. [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); Pui, Ching-Hon [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States)

    2007-11-15

    During the past three decades, improvements in the treatment of childhood leukemia have resulted in high cure rates, particularly for acute lymphoblastic leukemia (ALL). Unfortunately, successful therapy has come with a price, as significant morbidity can result from neurological affects which harm the brain and spinal cord. The expectation and hope is that chemotherapy, as a primary means of CNS therapy, will result in acceptable disease control with less CNS morbidity than has been observed with combinations of chemotherapy and radiotherapy over the past several decades. In this review we discuss the poignant, historical aspects of CNS leukemia therapy, outline current methods of systemic and CNS leukemia therapy, and present imaging findings we have encountered in childhood leukemia patients with a variety of acute neurological conditions. A major objective of our research is to understand the neuroimaging correlates of acute and chronic effects of cancer and therapy. Specific features related to CNS leukemia and associated short-term toxicities, both disease- and therapy-related, are emphasized in this review with the specific neuroimaging findings. Specific CNS findings are similarly important when treating acute myelogenous leukemia (AML), and details of leukemic involvement and toxicities are also presented in this entity. Despite contemporary treatment approaches which favor the use of chemotherapy (including intrathecal therapy) over radiotherapy in the treatment of CNS leukemia, children still occasionally experience morbid neurotoxicity. Standard neuroimaging is sufficient to identify a variety of neurotoxic sequelae in children, and often suggest specific etiologies. Specific neuroimaging findings frequently indicate a need to alter antileukemia therapy. It is important to appreciate that intrathecal and high doses of systemic chemotherapy are not innocuous and are associated with acute, specific, recognizable, and often serious neurological

  18. Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome

    NARCIS (Netherlands)

    Zwaan, CM; Kaspers, GJL; Pieters, R; Hahlen, K; Janka-Schaub, GE; van Zantwijk, CH; Huismans, DR; de Vries, E; Rots, MG; Peters, GJ; Jansen, G; Creutzig, U; Veerman, AJP

    2002-01-01

    Children with Down syndrome (DS) have an increased risk for leukemia. The prognosis for DS acute myeloid leukemia (AML) is better than for non-DS AML, but the clinical outcome of DS acute lymphoblastic leukemia (ALL) is equal to that of non-DS ALL. Differences in prognosis may reflect differences in

  19. Myelodysplastic Syndrome with Myelofibrosis Transformed to a Precursor B-Cell Acute Lymphoblastic Leukemia: A Case Report with Review of the Literature

    OpenAIRE

    2012-01-01

    Myelodysplastic syndromes (MDS) comprise a group of heterogeneous clonal hematopoietic cell disorders characterized by cytopenias, bone marrow hypercellularity, and increased risk of transformation to acute leukemias. MDS usually transformed to acute myeloid leukemia, and transformation to acute lymphoblastic leukemia (ALL) is rare. Herein, we report a unique patient who presented with MDS with myelofibrosis. Two months after the initial diagnosis, she progressed to a precursor B-cell acute l...

  20. Proposal for the standardization of flow cytometry protocols to detect minimal residual disease in acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Maura Rosane Valério Ikoma

    2015-12-01

    Full Text Available ABSTRACT Minimal residual disease is the most powerful predictor of outcome in acute leukemia and is useful in therapeutic stratification for acute lymphoblastic leukemia protocols. Nowadays, the most reliable methods for studying minimal residual disease in acute lymphoblastic leukemia are multiparametric flow cytometry and polymerase chain reaction. Both provide similar results at a minimal residual disease level of 0.01% of normal cells, that is, detection of one leukemic cell in up to 10,000 normal nucleated cells. Currently, therapeutic protocols establish the minimal residual disease threshold value at the most informative time points according to the appropriate methodology employed. The expertise of the laboratory in a cancer center or a cooperative group could be the most important factor in determining which method should be used. In Brazil, multiparametric flow cytometry laboratories are available in most leukemia treatment centers, but multiparametric flow cytometry processes must be standardized for minimal residual disease investigations in order to offer reliable and reproducible results that ensure quality in the clinical application of the method. The Minimal Residual Disease Working Group of the Brazilian Society of Bone Marrow Transplantation (SBTMO was created with that aim. This paper presents recommendations for the detection of minimal residual disease in acute lymphoblastic leukemia based on the literature and expertise of the laboratories who participated in this consensus, including pre-analytical and analytical methods. This paper also recommends that both multiparametric flow cytometry and polymerase chain reaction are complementary methods, and so more laboratories with expertise in immunoglobulin/T cell receptor (Ig/TCR gene assays are necessary in Brazil.

  1. Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or High-Risk Myelodysplastic Syndrome

    Science.gov (United States)

    2016-07-18

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

  2. RNA sequencing unravels the genetics of refractory/relapsed T-cell acute lymphoblastic leukemia. Prognostic and therapeutic implications

    Science.gov (United States)

    Gianfelici, Valentina; Chiaretti, Sabina; Demeyer, Sofie; Di Giacomo, Filomena; Messina, Monica; La Starza, Roberta; Peragine, Nadia; Paoloni, Francesca; Geerdens, Ellen; Pierini, Valentina; Elia, Loredana; Mancini, Marco; De Propris, Maria Stefania; Apicella, Valerio; Gaidano, Gianluca; Testi, Anna Maria; Vitale, Antonella; Vignetti, Marco; Mecucci, Cristina; Guarini, Anna; Cools, Jan; Foà, Robin

    2016-01-01

    Despite therapeutic improvements, a sizable number of patients with T-cell acute lymphoblastic leukemia still have a poor outcome. To unravel the genomic background associated with refractoriness, we evaluated the transcriptome of 19 cases of refractory/early relapsed T-cell acute lymphoblastic leukemia (discovery cohort) by performing RNA-sequencing on diagnostic material. The incidence and prognostic impact of the most frequently mutated pathways were validated by Sanger sequencing on genomic DNA from diagnostic samples of an independent cohort of 49 cases (validation cohort), including refractory, relapsed and responsive cases. Combined gene expression and fusion transcript analyses in the discovery cohort revealed the presence of known oncogenes and identified novel rearrangements inducing overexpression, as well as inactivation of tumor suppressor genes. Mutation analysis identified JAK/STAT and RAS/PTEN as the most commonly disrupted pathways in patients with chemorefractory disease or early relapse, frequently in association with NOTCH1/FBXW7 mutations. The analysis on the validation cohort documented a significantly higher risk of relapse, inferior overall survival, disease-free survival and event-free survival in patients with JAK/STAT or RAS/PTEN alterations. Conversely, a significantly better survival was observed in patients harboring only NOTCH1/FBXW7 mutations: this favorable prognostic effect was abrogated by the presence of concomitant mutations. Preliminary in vitro assays on primary cells demonstrated sensitivity to specific inhibitors. These data document the negative prognostic impact of JAK/STAT and RAS/PTEN mutations in T-cell acute lymphoblastic leukemia and suggest the potential clinical application of JAK and PI3K/mTOR inhibitors in patients harboring mutations in these pathways. PMID:27151993

  3. Are parenting behaviors associated with child sleep problems during treatment for acute lymphoblastic leukemia?

    Science.gov (United States)

    McCarthy, Maria C; Bastiani, Jessica; Williams, Lauren K

    2016-07-01

    Sleep disturbance is a recognized common side effect in children treated for acute lymphoblastic leukemia (ALL). Although associated with treatment factors such as hospitalization and corticosteroids, sleep problems may also be influenced by modifiable environmental factors such as parenting behaviors. The purpose of this study was to examine sleep problems in children undergoing treatment for ALL compared to healthy children and whether parenting practices are associated with sleep difficulties. Parents of 73 children aged 2-6 years who were (1) in the maintenance phase of ALL treatment (ALL group, n = 43) or (2) had no major medical illness (healthy control group, n = 30) participated in the study. Parents completed questionnaires measuring their child's sleep behavior and their own parenting practices. Parents of children undergoing ALL treatment reported significantly more child sleep problems; 48% of children with ALL compared to 23% of healthy children had clinical levels of sleep disturbance. Parents of the ALL group also reported significantly more lax parenting practices and strategies associated with their child's sleep including co-sleeping, comforting activities, and offering food and drink in the bedroom. Results of multivariate regression analysis indicated that, after controlling for illness status, parent-child co-sleeping was significantly associated with child sleep difficulties. Strategies employed by parents during ALL treatment may be a potential modifiable intervention target that could result in improved child sleep behaviors. Future research aimed at developing and testing parenting interventions aimed to improve child sleep in the context of oncology treatment is warranted.

  4. Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Karol, Seth E; Yang, Wenjian; Van Driest, Sara L; Chang, Tamara Y; Kaste, Sue; Bowton, Erica; Basford, Melissa; Bastarache, Lisa; Roden, Dan M; Denny, Joshua C; Larsen, Eric; Winick, Naomi; Carroll, William L; Cheng, Cheng; Pei, Deqing; Fernandez, Christian A; Liu, Chengcheng; Smith, Colton; Loh, Mignon L; Raetz, Elizabeth A; Hunger, Stephen P; Scheet, Paul; Jeha, Sima; Pui, Ching-Hon; Evans, William E; Devidas, Meenakshi; Mattano, Leonard A; Relling, Mary V

    2015-10-08

    Glucocorticoids are important therapy for acute lymphoblastic leukemia (ALL) and their major adverse effect is osteonecrosis. Our goal was to identify genetic and nongenetic risk factors for osteonecrosis. We performed a genome-wide association study of single nucleotide polymorphisms (SNPs) in a discovery cohort comprising 2285 children with ALL, treated on the Children's Oncology Group AALL0232 protocol (NCT00075725), adjusting for covariates. The minor allele at SNP rs10989692 (near the glutamate receptor GRIN3A locus) was associated with osteonecrosis (hazard ratio = 2.03; P = 3.59 × 10(-7)). The association was supported by 2 replication cohorts, including 361 children with ALL on St. Jude's Total XV protocol (NCT00137111) and 309 non-ALL patients from Vanderbilt University's BioVU repository treated with glucocorticoids (odds ratio [OR] = 1.87 and 2.26; P = .063 and .0074, respectively). In a meta-analysis, rs10989692 was also highest ranked (P = 2.68 × 10(-8)), and the glutamate pathway was the top ranked pathway (P = 9.8 × 10(-4)). Osteonecrosis-associated glutamate receptor variants were also associated with other vascular phenotypes including cerebral ischemia (OR = 1.64; P = 2.5 × 10(-3)), and arterial embolism and thrombosis (OR = 1.88; P = 4.2 × 10(-3)). In conclusion, osteonecrosis was associated with inherited variations near glutamate receptor genes. Further understanding this association may allow interventions to decrease osteonecrosis. These trials are registered at www.clinicaltrials.gov as #NCT00075725 and #NCT00137111.

  5. Computer-aided diagnosis of leukoencephalopathy in children treated for acute lymphoblastic leukemia

    Science.gov (United States)

    Glass, John O.; Li, Chin-Shang; Helton, Kathleen J.; Reddick, Wilburn E.

    2005-04-01

    The purpose of this study was to use objective quantitative MR imaging methods to develop a computer-aided diagnosis tool to differentiate white matter (WM) hyperintensities as either leukoencephalopathy (LE) or normal maturational processes in children treated for acute lymphoblastic leukemia with intravenous high dose methotrexate. A combined imaging set consisting of T1, T2, PD, and FLAIR MR images and WM, gray matter, and cerebrospinal fluid a priori maps from a spatially normalized atlas were analyzed with a neural network segmentation based on a Kohonen Self-Organizing Map. Segmented regions were manually classified to identify the most hyperintense WM region and the normal appearing genu region. Signal intensity differences normalized to the genu within each examination were generated for two time points in 203 children. An unsupervised hierarchical clustering algorithm with the agglomeration method of McQuitty was used to divide data from the first examination into normal appearing or LE groups. A C-support vector machine (C-SVM) was then trained on the first examination data and used to classify the data from the second examination. The overall accuracy of the computer-aided detection tool was 83.5% (299/358) with sensitivity to normal WM of 86.9% (199/229) and specificity to LE of 77.5% (100/129) when compared to the readings of two expert observers. These results suggest that subtle therapy-induced leukoencephalopathy can be objectively and reproducibly detected in children treated for cancer using this computer-aided detection approach based on relative differences in quantitative signal intensity measures normalized within each examination.

  6. Epigenetic inactivation of Notch-Hes pathway in human B-cell acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Shao-Qing Kuang

    Full Text Available The Notch pathway can have both oncogenic and tumor suppressor roles, depending on cell context. For example, Notch signaling promotes T cell differentiation and is leukemogenic in T cells, whereas it inhibits early B cell differentiation and acts as a tumor suppressor in B cell leukemia where it induces growth arrest and apoptosis. The regulatory mechanisms that contribute to these opposing roles are not understood. Aberrant promoter DNA methylation and histone modifications are associated with silencing of tumor suppressor genes and have been implicated in leukemogenesis. Using methylated CpG island amplification (MCA/DNA promoter microarray, we identified Notch3 and Hes5 as hypermethylated in human B cell acute lymphoblastic leukemia (ALL. We investigated the methylation status of other Notch pathway genes by bisulfite pyrosequencing. Notch3, JAG1, Hes2, Hes4 and Hes5 were frequently hypermethylated in B leukemia cell lines and primary B-ALL, in contrast to T-ALL cell lines and patient samples. Aberrant methylation of Notch3 and Hes5 in B-ALL was associated with gene silencing and was accompanied by decrease of H3K4 trimethylation and H3K9 acetylation and gain of H3K9 trimethylation and H3K27 trimethylation. 5-aza-2'-deoxycytidine treatment restored Hes5 expression and decreased promoter hypermethylation in most leukemia cell lines and primary B-ALL samples. Restoration of Hes5 expression by lentiviral transduction resulted in growth arrest and apoptosis in Hes5 negative B-ALL cells but not in Hes5 expressing T-ALL cells. These data suggest that epigenetic modifications are implicated in silencing of tumor suppressor of Notch/Hes pathway in B-ALL.

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

    Directory of Open Access Journals (Sweden)

    Francis Richard W

    2010-04-01

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

  8. The prognostic value of glucocorticoid receptors for adult acute lymphoblastic leukemia

    Science.gov (United States)

    EL-Maghraby, Shereen M.; Kandil, Noha S.; El-Bendary, Waleed R.

    2015-01-01

    Background Therapeutic protocols used in adult acute lymphoblastic leukemia (ALL) are widely variable, and glucocorticoids (GCs) are essential components in ALL treatment. Therefore, this study aimed to evaluate the distribution of prominent glucocorticoid receptor (GR) gene polymorphic variants among adult ALL patients. We also investigated the association between GR messenger ribonucleic acid (mRNA) isoform expressions and the response to chemotherapy. Methods Fifty-two newly diagnosed Philadelphia-negative adult ALL patients and 30 healthy control subjects were enrolled in this study. Genotyping was carried out using a polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis. GR mRNA isoform expressions were assayed by quantitative real-time PCR. Results ALL patients in this study had a median age of 34 years (range, 18-75). GRα expression was associated with complete remission (P=0.03), while GRγ mRNA expression was significantly higher in GC resistant patients (P=0.032) and in non-responders (P=0.019). However, there were no significant associations with GC resistance. The BclI polymorphic variant of the GR gene was the most frequent in adult ALL patients and was not associated with the GC response. Both higher GRα expression and lower GRγ expression were associated with achievement of complete remission, while higher GRγ expression was associated with GC-resistance. Conclusion Our data suggest that the level of GR isoform expression may be useful in predicting GC response, achievement of complete remission, and better event-free survival in ALL patients. However, further evaluation with a larger cohort of patients is warranted. PMID:26770951

  9. SLAM family predicting the initiation potential of human acute lymphoblastic leukemia in NOD/SCID mice

    Institute of Scientific and Technical Information of China (English)

    WANG Na; ZHOU Jian-feng; HUANG Liang; XIAO Fei; LIU Jin-ping; WANG Di; GENG Zhe; WANG Jin; MA Shu-yan; SHU Li-li; CHEN Tai-ping

    2011-01-01

    Background The SLAM family recently has been reported to show an important biological role in lymphocyte development and immunological function, and it is efficient to highly purify hematopoietic stem cells using a simple combination of SLAM family members. To elucidate the presence of this family on acute lymphoblastic leukemia (ALL),as well as its relationship with the leukemia-initiating potential, we analyzed the expression pattern of this family members on human ALL progenitor cells, combined with serial xenotransplantation assay.Methods Expression analysis was carried out by flow cytometry. We combined the expression pattern of human CD150,CD244 and CD48 with serial xenotransplantation of B-ALL progenitor cells to indicate their relationship.Results CD48 and CD244 were expressed on most B-ALL progenitor cells, the percentage being (93.08±6.46)% and (63.37±29.31)%, respectively. Interestingly, the proportion of CD150+ cells declined obviously in engrafted cases ((24.94±7.32)%) compared with non-engrafted cases ((77.54±5.93)%, P <0.01), which indicated that only blast cells with low percentage of CD150+ population were able to reconstitute leukemia into primary, secondary and tertiary NOD/SCID mice.Conclusions SLAM family members are present on B-ALL progenitor cells and the leukemia-initiating potential of leukemic blasts is correlated negatively with the proportion of CD150+ cells, the percentage of which can serve as a useful predictor for engraftment success of B-ALL to immune deficient mice.

  10. Hypertension, high-dose corticosteroids, and renal infiltration in children with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Andry Juliansen

    2014-11-01

    Full Text Available Background Hypertension is a rarely recognized complication of acute lymphoblastic leukemia (ALL. The incidence of hypertension in ALL patients in Indonesia remains unknown, but the most common risk factors are corticosteroid use during induction-phase chemotherapy and renal leukemic infiltration. Objective To determine the incidence of hypertension in children with ALL, and to assess for associations of high-dose corticosteroids, renal infiltration, and hyperleukocytosis to hypertension. Methods This was a cross-sectional study involving 100 children aged 2-18 years. Subjects were newly diagnosed ALL patients and those underwent induction-phase chemotherapy in the Pediatric Ward or Outpatient Clinic at Cipto Mangunkusumo or Dharmais Hospitals. Results Hypertension occurred in 6 (10% of 60 newly diagnosed ALL patients and 8 (20% of 40 patients who had received high-dose corticosteroids, but the difference was not statistically significant (OR=2.25; 95%CI 0.72 to 7.07; P=0.239. Hypertension was reported in 8 of 29 subjects who received dexamethasone, but in none of the subjects who received prednisone. However, the difference in these subgroups was also not statistically significant. Renal enlargement was found in 1 of 14 hypertensive patients, but it was not associated with hypertension (OR=0.80; 95%CI 0.52 to 1.24; P=0.417. Hyperleukocytosis was also not associated with hypertension (OR= 0.79; 95% CI 0.20 to 3.11; P=1.000. Conclusion The incidence of hypertension in ALL patients was 14%. Hypertension is not associated with renal infiltration or hyperleukocytosis. Furthermore, hypertension is not associated with corticosteroid dose, though is found only in subjects who receive dexamethasone. [Paediatr Indones. 2014;54:372-6.].

  11. The Second-Generation Exportin-1 Inhibitor KPT-8602 Demonstrates Potent Activity against Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Vercruysse, Thomas; De Bie, Jolien; Neggers, Jasper E; Jacquemyn, Maarten; Vanstreels, Els; Schmid-Burgk, Jonathan L; Hornung, Veit; Baloglu, Erkan; Landesman, Yosef; Senapedis, William; Shacham, Sharon; Dagklis, Antonis; Cools, Jan; Daelemans, Dirk

    2016-10-25

    Purpose: Human exportin-1 (XPO1) is the key nuclear-cytoplasmic transport protein that exports different cargo proteins out of the nucleus. Inducing nuclear accumulation of these proteins by inhibiting XPO1 causes cancer cell death. First clinical validation of pharmacological inhibition of XPO1 was obtained with the Selective Inhibitor of Nuclear Export (SINE) compound selinexor (KPT-330) demonstrating activity in phase-II/IIb clinical trials when dosed 1 to 3 times weekly. The second-generation SINE compound KPT-8602 shows improved tolerability and can be dosed daily. Here, we investigate and validate the drug-target interaction of KPT-8602 and explore its activity against acute lymphoblastic leukemia (ALL).Experimental Design: We examined the effect of KPT-8602 on XPO1 function and XPO1-cargo as well as on a panel of leukemia cell lines. Mutant XPO1 leukemia cells were designed to validate KPT-8602's drug-target interaction. In vivo, anti-ALL activity was measured in a mouse ALL model and patient-derived ALL xenograft models.Results: KPT-8602 induced caspase-dependent apoptosis in a panel of leukemic cell lines in vitro Using CRISPR/Cas9 genome editing, we demonstrated the specificity of KPT-8602 for cysteine 528 in the cargo-binding groove of XPO1 and validated the drug target interaction. In vivo, KPT-8602 showed potent anti-leukemia activity in a mouse ALL model as well as in patient-derived T- and B-ALL xenograft models without affecting normal hematopoiesis.Conclusions: KPT-8602 is highly specific for XPO1 inhibition and demonstrates potent anti-leukemic activity supporting clinical application of the second-generation SINE compound for the treatment of ALL. Clin Cancer Res; 1-14. ©2016 AACR.

  12. [Clinical study of 32 patients with adult Philadelphia chromosome-positive acute lymphoblastic leukemia].

    Science.gov (United States)

    Chen, Xiao-Yun; Zheng, Yong-Liang; Chen, Yi-Jian

    2014-12-01

    This study was aimed to evaluate the efficacy and safety of imatinib in the treatment of patients with adult Ph chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). A total of 32 diagnosed adult Ph(+)ALL patients from July 2007 to February 2014 in our hospital were retrospectively analyzed and were divided into two groups: imatinib plus chemotherapy group and traditional chemotherapy group. The differences between two groups were analysed in disease-free survival time (DFS), overall survival time (OS) and toxicity. The G banding technigue was used to analyse the karyotype, and the flow cytometry was applyed to detect the immune markers on surface of cells. The results showed that all patients expressed B cell and hematopietic stem/progenitor cell immune markers, out of them 21 patients (65.6%) were with myeloid antigens, 27 patients with simple Ph (+) phenotype and 5 patients with additional chromosome abnormality. The DFS and OS of the imatinib group were statistically longer than those of the traditional chemotherapy group (14.3 ± 4.7 months vs 10.7 ± 3.8 months) (P 0.05)). It is concluded that the all cases of adult Ph(+)ALL are with B cell phenotype and express hematopietic stem/progenitor cell antigen. They often accompanied by expression of myeloid antigens and additonal chromosome abnormality in genetics. The combination of imatinib with chemotherapy can prolong remission time and survival time for patients of non-hematopietic stem cell transplantation on the basis of no notably increasing the toxic effects.

  13. Cytotoxic and apoptotic effects of prenylflavonoid artonin B in human acute lymphoblastic leukemia cells

    Institute of Scientific and Technical Information of China (English)

    Chun-chung LEE; Chun-nan LIN; Guey-mei JOW

    2006-01-01

    Aim: To investigate the anticancer effects and molecular mechanism of artonin B on the human acute lymphoblastic leukemia CCRF-CEM cells compared with other prenylflavonoid compounds. Methods: The effects of four prenylflavonoids on the growth of CCRF-CEM and HaCa cells were studied by 3-(4,5)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Apoptosis were detected through Hoechst 33258 staining. The effect of artonin B on the cell cycle of CCRF-CEM cells were studied by propidium iodide method. The change in mitochondrial membrane potential was detected by rohdamine 123 staining. The cytochrome c release and caspase 3 activity were checked by immunoassay kits, respectively. The expression of Bcl-2 family proteins was detected by Western blot. Results: Our data revealed that artonin B strongly induced human CCRF-CEM leukemia cell death in a dose- and time-dependent manner by MTT assay, but not on normal epithelia cells (HaCa cells). Artonin B-induced cell death was considered to be apoptotic by observing the typical apoptotic morphological change by Hoechst 33258 staining. The induction of human CCRF-CEM leukemia cancer cell death was caused by an induction of apoptosis through mitochondrial membrane potential change, cytochrome c release, sub-G1 proportion increase, downregulation of Bcl-2 expression, upregulation of Bax and Bak expression and activation of caspase 3 pathways. Conclusion: These results clearly demonstrated that artonin B is able to inhibit proliferation by induction of hypoploid cells and cell apoptosis. Moreover, the anticancer effects of artonin B were related to mitochondrial pathway and caspase 3 activation in human CCRF-CEM leukemia cells.

  14. Nutritional state alterations in children with acute lymphoblastic leukemia during induction and consolidation of chemotherapy.

    Science.gov (United States)

    Mejía-Arangure, J M; Fajardo-Gutíerrez, A; Bernáldez-Ríos, R; Rodríguez-Zepeda, M C; Espinoza-Hernández, L; Martínez-García, M C

    1997-01-01

    The objective of the study was to determine if children with high risk acute lymphoblastic leukemia (ALL) exhibit higher frequency of alterations in nutritional state during the phases of induction and consolidation of chemotherapy than children with low risk ALL, based on the arm muscle area. The design was concurrent comparative cohorts. It was performed at pediatric hematology service of the Hospital General del Centro Médico Nacional "La Raza" and hematology service of the Hospital de Pediatría del Centro Médico Nacional "Siglo XXI". One hundred-five patients were incorporated into the study: 53 with high risk (HR) ALL and 52 with low risk (LR) ALL. Basal measurements of arm circumference and tricipital skinfold were surveyed monthly (for 3 months) by standardized personnel. Altered nutritional state during follow-up was defined as the loss of 10% or more of the arm muscular area (AMA) measured at diagnosis. Statistics of proportion analysis with a significance level of 0.05 and relative risk (RR) with confidence intervals (CI) were calculated. In the first month the RR was 0.77 (CI 0.31-1.87); the LR group was the most affected. In the second month the RR was 7.31 (CI 1.41-38.03); the most affected group was the HR. In the third month the RR was 1.77 (CI 0.60-4.92); the HR group was the most affected. High-risk patients show a higher frequency of nutritional state alterations reflected in AMA during the second month after diagnosis. This may be caused by the more aggressive chemotherapy received by these patients.

  15. Targeting FLT3 in primary MLL-gene-rearranged infant acute lymphoblastic leukemia.

    Science.gov (United States)

    Stam, Ronald W; den Boer, Monique L; Schneider, Pauline; Nollau, Peter; Horstmann, Martin; Beverloo, H Berna; van der Voort, Ella; Valsecchi, Maria G; de Lorenzo, Paola; Sallan, Stephen E; Armstrong, Scott A; Pieters, Rob

    2005-10-01

    Acute lymphoblastic leukemia (ALL) in infants is characterized by rearrangements of the mixed lineage leukemia (MLL) gene, drug resistance, and a poor treatment outcome. Therefore, novel therapeutic strategies are needed to improve prognosis. Recently, we showed that FLT3 is highly expressed in MLL rearranged ALL (MLL). Here we demonstrate FLT3 expression in infants with MLL (n = 41) to be significantly higher compared to both infant (n = 8; P < .001) and noninfant patients with ALL (n = 23; P = .001) carrying germline MLL genes. Furthermore, leukemic cells from infants with MLL were significantly more sensitive to the Fms-like tyrosine kinase 3 (FLT3) inhibitor PKC412 (N-benzoyl staurosporine) than noninfant ALL cells, and at least as sensitive as internal tandem duplication-positive (ITD+) AML cells. Surprisingly, activation loop mutations only occurred in about 3% (1 of 36) of the cases and no FLT3/ITDs were observed. However, measuring FLT3 phosphorylation in infants with MLL expressing varying levels of wild-type FLT3 revealed that high-level FLT3 expression is associated with ligand-independent FLT3 activation. This suggests that infant MLL cells displaying activated FLT3 as a result of overexpression can be targeted by FLT3 inhibitors such as PKC412. However, at concentrations of PKC412 minimally required to fully inhibit FLT3 phosphorylation, the cytotoxic effects were only fractional. Thus, PKC412-induced apoptosis in infant MLL cells is unlikely to be a consequence of FLT3 inhibition alone but may involve inhibition of multiple other kinases by this drug.

  16. Activity of the Aurora kinase inhibitor VX-680 against Bcr/Abl-positive acute lymphoblastic leukemias.

    Science.gov (United States)

    Fei, Fei; Stoddart, Sonia; Groffen, John; Heisterkamp, Nora

    2010-05-01

    The emergence of resistance to tyrosine kinase inhibitors due to point mutations in Bcr/Abl is a challenging problem for Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) patients, especially for those with the T315I mutation, against which neither nilotinib or dasatinib shows significant activity. VX-680 is a pan-Aurora kinase inhibitor active against all Bcr/Abl proteins but has not been extensively examined in preclinical models of Ph-positive ALL. Here, we have tested VX-680 for the treatment of Bcr/Abl-positive ALL when leukemic cells are protected by the presence of stroma. Under these conditions, VX-680 showed significant effects on primary human Ph-positive ALL cells both with and without the T315I mutation, including ablation of tyrosine phosphorylation downstream of Bcr/Abl, decreased viability, and induction of apoptosis. However, drug treatment of human Ph-positive ALL cells for 3 days followed by drug removal allowed the outgrowth of abnormal cells 21 days later, and on culture of mouse Bcr/Abl ALL cells on stroma with lower concentrations of VX-680, drug-resistant cells emerged. Combined treatment of human ALL cells lacking the T315I mutation with both VX-680 and dasatinib caused significantly more cytotoxicity than each drug alone. We suggest that use of VX-680 together with a second effective drug as first-line treatment for Ph-positive ALL is likely to be safer and more useful than second-line treatment with VX-680 as monotherapy for drug-resistant T315I Ph-positive ALL.

  17. CT and MR imaging findings of appendiceal and hepatic mucormycosis in a patient with acute T-lymphoblastic leukemia

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    Choi, Seo Youn; Lee, Min Hee; Lee, Hae Kyung; Yi, Boem Ha; Chin, Su Sie; Park, Seong Kyu; Chung, Jun Chul [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of)

    2015-11-15

    Fungal infections occur in severely immunocompromised patients having profound and prolonged neutropenia. Here, we report a case of a 41-year-old female who, at the conclusion of induction chemotherapy for acute T-lymphoblastic leukemia, developed angioinvasive mucormycosis involving the appendix and liver, which presented as abdominal pain. This case is the first to provide detailed computed tomography and magnetic resonance imaging findings of angioinvasive appendiceal and hepatic mucormycosis. The implications of these findings as well as the diagnosis and management of mucormycosis, is further discussed.

  18. Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia.

    Science.gov (United States)

    Karol, Seth E; Mattano, Leonard A; Yang, Wenjian; Maloney, Kelly W; Smith, Colton; Liu, ChengCheng; Ramsey, Laura B; Fernandez, Christian A; Chang, Tamara Y; Neale, Geoffrey; Cheng, Cheng; Mardis, Elaine; Fulton, Robert; Scheet, Paul; San Lucas, F Anthony; Larsen, Eric C; Loh, Mignon L; Raetz, Elizabeth A; Hunger, Stephen P; Devidas, Meenakshi; Relling, Mary V

    2016-02-04

    Osteonecrosis is a dose-limiting toxicity in the treatment of pediatric acute lymphoblastic leukemia (ALL). Prior studies on the genetics of osteonecrosis have focused on patients ≥10 years of age, leaving the genetic risk factors for the larger group of children osteonecrosis in children osteonecrosis and 287 controls treated on Children's Oncology Group (COG) standard-risk ALL protocol AALL0331 (NCT00103285, https://clinicaltrials.gov/ct2/show/NCT00103285), with results tested for replication in 817 children osteonecrosis.

  19. Renal infarction secondary to invasive aspergillosis in a 5-year-old girl with acute lymphoblastic leukemia.

    Science.gov (United States)

    Lee, Ju Hyun; Im, Soo Ah; Cho, Bin

    2014-07-01

    Aspergillus species have angioinvasive properties and can involve extrapulmonary organs by hematogenous spread from the lungs. However, renal involvement by Aspergillus is uncommon and is usually associated with the formation of abscesses. We report an unusual case of invasive renal aspergillosis presenting with extensive renal infarction in a 5-year-old girl with acute lymphoblastic leukemia. This case emphasizes the fact that renal aspergillosis initially presents with only renal infarction, and metastatic-embolism by invasive aspergillosis should be considered in differential diagnosis for any focal lesion of kidney in a patient with leukemia.

  20. Successful collection of peripheral blood stem cells from an infant with acute lymphoblastic leukemia using the Haemonetics V50.

    Science.gov (United States)

    Suzuki, N; Katoh, S; Kudoh, T; Yohtoh, Y; Chiba, S

    1992-12-01

    Peripheral blood stem cells (PBSC) were collected using the Haemonetics V50 from an 8 month old infant weighing 7.8 kg suffering from acute lymphoblastic leukemia in the first complete remission. Leukapheresis was performed according to an exchange transfusion procedure by the two arm method using only a single lumen Broviac catheter. No problem occurred in the patient during this procedure except for a reduction (by half) of the initial platelet count. This method enables one to collect PBSC very safely, even from infants, in a manner that is painless for patients.

  1. Bilateral Facial Nerve Palsy in Acute B Cell Lymphoblastic Leukemia: A Case Report and Review of the Literature.

    Science.gov (United States)

    Sen, Shiraj; Gupta, Arjun; Friedman, Paul; Naina, Harris V

    2016-06-01

    Acute lymphoblastic leukemia (ALL) is a haematological malignancy that can involve the central nervous system (CNS). Less than 10 % of patients with ALL have CNS involvement at presentation. The cranial nerve most commonly affected is cranial nerve VII although bilateral involvement is rare. Management and outcomes of these patients are not well understood. Moreover bilateral Bells palsy as a presenting symptom of ALL is extremely uncommon. We report a very unusual presentation of ALL with bilateral facial nerve palsy, and discuss the management strategies and outcomes for patients with ALL that present with cranial nerve palsies.

  2. Technical relapsed testicular irradiation for acute lymphoblastic leukemia; Tecnica de irradiacion para testiculos en recidiva de leucemia linfoblastica aguda

    Energy Technology Data Exchange (ETDEWEB)

    Velazquez Miranda, S.; Delgado Gil, M. M.; Ortiz Siedel, M.; Munoz Carmona, D. M.; Gomez-Barcelona, J.

    2011-07-01

    Testicular irradiation in children suffering from acute lymphoblastic leukemia presents difficulties in relation to daily positioning, dosimetry for dose homogenization of complex geometry and volume change during irradiation thereof. This can lead to significant deviations from the prescribed doses. In addition, the usual techniques often associated with unnecessary irradiation of pelvic simphysis, anus and perineum. This, in the case of pediatric patients, is of great importance, since doses in the vicinity of 20 Gy are associated with a deviation of bone growth, low testosterone levels around 24 Gy and high rates of generation of second tumors. To overcome these problems we propose a special restraint in prone and non-coplanar irradiation.

  3. Functional analyses of Src-like adaptor (SLA), a glucocorticoid-regulated gene in acute lymphoblastic leukemia.

    Science.gov (United States)

    Mansha, Muhammad; Carlet, Michela; Ploner, Christian; Gruber, Georg; Wasim, Muhammad; Wiegers, Gerrit Jan; Rainer, Johannes; Geley, Stephan; Kofler, Reinhard

    2010-04-01

    Glucocorticoids (GCs) cause apoptosis and cell cycle arrest in lymphoid cells and are used in the therapy of lymphoid malignancies. SLA (Src-like-adaptor), an inhibitor of T- and B-cell receptor signaling, is a promising candidate derived from expression profiling analyses in children with acute lymphoblastic leukemia (ALL). Over-expression and knock-down experiments in ALL in vitro model revealed that transgenic SLA alone had no effect on survival or cell cycle progression, nor did it affect sensitivity to, or kinetics of, GC-induced apoptosis. Although SLA is a prominent GC response gene, it does not seem to contribute to the anti-leukemic effects of GC.

  4. Mucormycosis Rhinosinusitis at Diagnosis of Acute Lymphoblastic Leukemia: Diagnostics and Management Challenges in a Low-Middle-income Country.

    Science.gov (United States)

    Mandegari, Elham; Fu, Ligia; Arambú, Carolina; Montoya, Sandra; Peña, Armando; Johnson, Kyle M; Perfect, John R; Caniza, Miguela A

    2015-04-01

    We present the case of an adolescent with mucor rhinosinusitis diagnosed concomitantly with acute lymphoblastic leukemia at a hospital in Tegucigalpa, Honduras. We also discuss the challenges faced in the dual management of hematologic malignancies and invasive fungal disease in a low-middle-income country, such as access to diagnostics, immunosuppressants, imaging, and antifungals. Despite these shortcomings, the patient was successfully treated for both the diseases. Low-middle-income country hospitals can effectively treat invasive fungal diseases by providing adequate diagnostic and support services, which can improve the outcomes of pediatric cancer patients.

  5. Recurrent Intrathecal Methotrexate Induced Neurotoxicity in an Adolescent with Acute Lymphoblastic Leukemia: Serial Clinical and Radiologic Findings

    Science.gov (United States)

    Brugnoletti, Fulvia; Morris, E. Brannon; Laningham, Fred H.; Patay, Zoltán; Pauley, Jennifer L; Pui, Ching-Hon; Jeha, Sima; Inaba, Hiroto

    2008-01-01

    Systemic and intrathecal methotrexate (MTX) are integral components of acute lymphoblastic leukemia (ALL) therapy, but can be associated with neurotoxicity. We describe here the case of an adolescent male with T-cell ALL who developed recurrent episodes of subacute neurotoxicity characterized by slurred speech, emotional lability, and hemiparesis after intrathecal MTX administration. Serial magnetic resonance imaging with diffusion-weighted imaging showed recurrent areas of restricted diffusion within cerebral hemispheric white matter, which correlated chronologically with the administration of intrathecal therapy and severity of clinical symptoms. Resolution of diffusion abnormalities did not preclude further toxicity and a large lesion could cause persisting symptoms. PMID:18831032

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

    Science.gov (United States)

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

    2016-04-25

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

  7. Fatal course of pulmonary Absidia sp. infection in a 4-year-old girl undergoing treatment for acute lymphoblastic leukemia.

    Science.gov (United States)

    Krauze, Agnieszka; Krenke, Katarzyna; Matysiak, Michal; Kulus, Marek

    2005-07-01

    Absidia sp. is a rare etiologic agent responsible for infectious complications in immunosuppressed patients. The authors describe a 4-year-old girl with acute lymphoblastic leukemia complicated with pleuropneumonia caused by an Absidia infection during the induction of remission. A review of the published reports in current literature is included for comparison. To the authors' knowledge only six cases of primary pulmonary absidiomycosis have been published. Despite its uncommon pulmonary presentation, mucormycosis should be considered in patients with an immunosuppressing illness and positive risk factors and when a pulmonary lesion is not responding to appropriate antibiotic therapy.

  8. The role of 18F-FDG PET/CT in pediatric lymph-node acute lymphoblastic leukemia involvement.

    Science.gov (United States)

    Cistaro, Angelina; Saglio, Francesco; Asaftei, Sebastian; Fania, Piercarlo; Berger, Massimo; Fagioli, Franca

    2011-01-01

    In pediatric oncology, positron emission tomography/computed tomography (PET/CT) is emerging as an essential diagnostic tool in characterizing suspicious neoplastic lesions and staging malignant diseases. Most studies regarding the possible role of FDG-PET/CT in the management of acute lymphoblastic leukemia (ALL) patients are limited to adults. Here we report a pediatric patient with recurrent ALL, in which FDG-PET/CT was used both to define more precisely the cause of lymphadenopathy and to assess the effect of the second-line therapy.

  9. D-HPLC analysis of the entire FLT3 gene in MLL rearranged and hyperdiploid acute lymphoblastic leukemia.

    Science.gov (United States)

    Stam, Ronald W; den Boer, Monique L; Schneider, Pauline; Meier, Marrit; Beverloo, H Berna; Pieters, Rob

    2007-11-01

    MLL rearranged and hyperdiploid acute lymphoblastic leukemia (ALL) are characterized by high-level FLT3 expression and constitutive FLT3 activation. As known activating FLT3 mutations are often absent in these patients, we screened the entire FLT3 coding sequence in MLL rearranged and hyperdiploid ALL cases for yet unidentified additional genetic alterations using denaturing D-HPLC. Both in MLL rearranged and hyperdiploid ALL we found that a small minority of samples, 7% and 10% respectively, carried genetic alterations. Although some of these alterations may induce FLT3 activation, the majority of these patients carry wild-type FLT3 genes.

  10. Acute Necrotizing Encephalopathy of Childhood; A Case Report

    Directory of Open Access Journals (Sweden)

    Mohammad Reza SALEHIOMRAN

    2013-06-01

    Full Text Available How to Cite this Article: Salehi Omran MR, Nooreddini H, Baghdadi F. Acute Necrotizing Encephalopathy of Childhood; A Case Report. Iran J Child Neurol. 2013 Spring;7(2:51-54. AbstractAcute Necrotizing Encephalopathy of Childhood (ANEC is an atypical disease followed by respiratory or gastrointestinal infection, high fever, which is accompanied with rapid alteration of consciousness and seizures. This disease is seen nearly exclusively in East Asian infants and children who had previously a good health. Serial MRI examinations demonstrated symmetric lesions involving the thalami, brainstem, cerebellum, and white matter. This disease has a poor prognosis, often culminating in profound morbidity and mortality. A 22-month infant with ANEC hospitalized in Amirkola Children Hospital has been evaluated. References1. Mizuguchi M. Acute necrotizing encephalopathy of childhood: a novel form of acute encephalopathy prevalent in Japan and Taiwan. Brain Dev. 1997 Mar;19(2:81-92. Review.2. Wang HS, Huang SC. Acute necrotizing encephalopathy of childhood. Chang Gung Med J 2001 Jan;24(1:1-10.3. Campistol J, Gassió R, Pineda M, Fernandez-Alvarez E. Acute necrotizing encephalopathy of childhood (infantile bilateral  thalamic necrosis: two non-Japanese cases. Dev Med Child Neurol 1998 Nov;40(11:771-4.4. Ito Y, Ichiyama T, Kimura H, Shibata M, Ishiwada N, Kuroki H, Furukawa S, Morishima T. Detection of influenza virus RNA by reverse transcription-PCR and proinflammatory cytokines in influenza-virus-associated encephalopathy. J Med Virol 1999 Aug;58(4:420-5.5. Sugaya N. Influenza-associated encephalopathy in Japan. Semin Pediatr Infect Dis 2002 Apr;13(2:79-84. Review.6. Skelton BW, Hollingshead MC, Sledd AT, Phillips CD, Castillo M. Acute necrotizing encephalopathy of childhood: typical findings in an atypical disease. Pediatr Radiol 2008 Jul; 38(7:810-3.7. Wong AM, Simon EM, Zimmerman RA, Wang HS, Toh CH, Ng SH. Acute necrotizing encephalopathy of childhood

  11. Incidence, risk factors, and treatment outcome of symptomatic osteonecrosis in Taiwanese children with acute lymphoblastic leukemia: a retrospective cohort study of 245 patients in a single institution.

    Science.gov (United States)

    Chen, Shih-Hsiang; Chang, Tsung-Yen; Jaing, Tang-Her; Lee, Mel S; Wang, Chao-Jan; Hung, Iou-Jih; Yang, Chao-Ping

    2015-07-01

    Osteonecrosis (ON) is a potentially disabling complication encountered in children who receive chemotherapy for acute lymphoblastic leukemia (ALL). Considering the possible effect of ethnic difference on the clinical features of symptomatic ON in pediatric ALL, we retrospectively evaluated 245 children with ALL who were treated at Chang Gung Memorial Hospital, Linkou, between 2002 and 2011. Six (2.4 %) patients developed symptomatic ON in a total of 17 sites during the follow-up period. Diagnosis of ON was confirmed by X-ray in seven, magnetic resonance imaging in two, and bone scan in three patients. The estimated cumulative incidence of symptomatic ON in newly diagnosed ALL was 3.4 % at 8 years. Four patients received ON-directed surgical interventions, including total hip replacement in three and arthroplasty in one. The incidence of ON was significantly higher among girls (P = 0.03), patients >10 years old (P = 2.2 × 10(-4)), and patients who had received more intensive chemotherapy regimen (P = 0.02). These results indicate that the incidence and risk factors in our institute were similar to those observed in Western countries. Future studies surveying the impact on the quality of life of childhood ALL survivors in Taiwan are warranted.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-15

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

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

    Science.gov (United States)

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

    2016-01-01

    Paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common cancer of childhood, yet little is known about BCP-ALL predisposition. In this study, in 2,187 cases of European ancestry and 5,543 controls, we discover and replicate a locus indexed by rs77728904 at 9p21.3 associated with BCP-ALL susceptibility (Pcombined=3.32 × 10−15, OR=1.72) and independent from rs3731217, the previously reported ALL-associated variant in this region. Of correlated SNPs tagged by this locus, only rs662463 is significant in African Americans, suggesting it is a plausible causative variant. Functional analysis shows that rs662463 is a cis-eQTL for CDKN2B, with the risk allele associated with lower expression, and suggests that rs662463 influences BCP-ALL risk by regulating CDKN2B expression through CEBPB signalling. Functional analysis of rs3731217 suggests it is associated with BCP-ALL by acting within a splicing regulatory element determining CDKN2A exon 3 usage (P=0.01). These findings provide new insights into the critical role of the CDKN2 locus in BCP-ALL aetiology. PMID:26868379

  14. A fatal case of acute pulmonary embolism caused by right ventricular masses of acute lymphoblastic lymphoma-leukemia in a 13 year old girl

    Directory of Open Access Journals (Sweden)

    Yu Mi Ko Ko

    2012-07-01

    Full Text Available We report a case of a 13-year-old girl with acute lymphoblastic lymphoma- leukemia, who presented with a cardiac metastasis in the right ventricle, resulting in a pulmonary embolism. At the time of her leukemia diagnosis, a cardiac mass was incidentally found. The differential diagnosis for this unusual cardiac mass included cardiac tumor, metastasis, vegetation, and thrombus. Empirical treatment was initiated, including anticoagulation and antibiotics. She underwent plasmapheresis and was administered oral prednisolone for her leukemia. Five days later, she experienced sudden hemodynamic collapse and required extracorporeal membrane oxygenation insertion and emergency surgery. These interventions proved futile, and the patient died. Pathology revealed that the cardiac mass comprised an aggregation of small, round, necrotic cells consistent with leukemia. This is the first known case of acute lymphoblastic leukemia presenting as a right ventricular mass, with consequent fatal acute pulmonary embolism. A cardiac mass in a child with acute leukemia merits investigation to rule out every possible etiology, including vegetation, thrombus, and even a mass of leukemic cells, which could result in the fatal complication of pulmonary embolism.

  15. Role of diffusion-weighted imaging for detecting bone marrow infiltration in skull in children with acute lymphoblastic leukemia

    Science.gov (United States)

    Cao, Weiguo; Liang, Changhong; Gen, Yungan; Wang, Chen; Zhao, Cailei; Sun, Longwei

    2016-01-01

    PURPOSE We aimed to determine whether diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) measurement can detect skull bone marrow infiltration in newly diagnosed acute lymphoblastic leukemia (ALL) children before therapy and normalization in complete remission after treatment. METHODS Fifty-one newly diagnosed acute lymphoblastic leukemia (ALL) patients and 30 healthy age-matched subjects were included. Cranial magnetic resonance imaging (MRI) scans were reviewed, and skull marrow ADC values were compared before treatment and in complete remission after therapy. RESULTS Skull marrow infiltration, manifested with abnormal DWI signals, was present in 37 patients (72.5%) before treatment. Of these, 23 (62.2%) showed scattered signal abnormalities and 14 (37.8%) showed a uniform abnormal signal pattern. Compared with the control group, ADC was significantly decreased in patients with ALL. DWI signal intensity and ADC normalized in patients with complete remission. CONCLUSION DWI is a useful and noninvasive tool for detecting skull infiltration in ALL children before treatment and normalization at complete remission after therapy, and it is superior to conventional MRI in terms of conspicuity of these lesions. DWI could be used as an MRI biomarker for evaluation of treatment in ALL children. PMID:27763327

  16. Antibody responses to Hepatitis B and measles-mumps-rubella vaccines in children who received chemotherapy for acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Simone Santana Viana

    2012-01-01

    Full Text Available OBJECTIVE: To evaluate viral vaccine antibody levels in children with acute lymphoblastic leukemia after chemotherapy and after vaccine booster doses. METHODS: Antibody levels against hepatitis B, rubella, measles and mumps vaccine antigens were evaluated in 33 children after completing chemotherapy (before and after vaccine booster doses and the results were compared to the data of 33 healthy children matched for gender, age and social class. RESULTS: After chemotherapy, 75.9%, 67.9%, 59.3% and 51.7% of the patients showed low antibody titers that would be unlikely to protect against exposure to measles, rubella, hepatitis B and mumps, respectively. After receiving a vaccine booster dose for these antigens the patients had high antibody levels consistent with potential protection against measles, mumps and hepatitis B, but not against rubella. CONCLUSION: Extra doses of measles-mumps-rubella plus hepatitis B vaccines are recommended in acute lymphoblastic leukemia patients submitted to treatment after hematologic recovery. After this, viral vaccine antibody levels should be verified to define the individual's protective status.

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

    Science.gov (United States)

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

    2013-11-01

    Survival for adults and children with acute lymphoblastic leukaemia has risen substantially in recent years because use of improved risk-directed treatments and supportive care has widened. In nearly all developed countries, multidisciplinary panels of leukaemia experts have formulated clinical practice guidelines in which standard treatment approaches are recommended on the basis of current evidence. However, those guidelines do not take into account resource limitations in low-income countries, including financial and technical challenges. In Asia, huge disparities in economy and infrastructure exist between countries, and even among different regions in some large countries. At a consensus session held as part of the 2013 Asian Oncology Summit in Bangkok, Thailand, a panel of experts summarised recommendations for management of adult and paediatric acute lymphoblastic leukaemia. Strategies were developed for Asian countries on the basis of available financial, skill, and logistical resources and were stratified in a four-tier system according to the resources available in a particular country or region (basic, limited, enhanced, and maximum).

  18. Profile of blinatumomab and its potential in the treatment of relapsed/refractory acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Ribera JM

    2015-06-01

    Full Text Available Josep-Maria Ribera, Albert Ferrer, Jordi Ribera, Eulàlia GenescàClinical Hematology Department, ICO-Hospital Germans Trias i Pujol, Josep Carreras Research Institute, Universitat Autònoma de Barcelona, Badalona, SpainAbstract: The CD19 marker is expressed on the surface of normal and malignant immature or mature B-cells. On the other hand, immunotherapy involving T-cells is a promising modality of treatment for many neoplastic diseases including leukemias and lymphomas. The CD19/CD3-bispecific T-cell-engaging (BiTE® monoclonal antibody blinatumomab can transiently engage cytotoxic T-cells to CD19+ target B-cells inducing serial perforin-mediated lysis. In the first clinical trial, blinatumomab showed efficacy in non-Hodgkin’s lymphomas, but the most important trials have been conducted in relapsed/refractory (R/R acute lymphoblastic leukemia (ALL and in ALL with minimal residual disease. Encouraging reports on the activity of blinatumomab in R/R Philadelphia chromosome-negative B-cell precursor ALL led to its approval by the US Food and Drug Administration on December 3, 2014 after an accelerated review process. This review focuses on the profile of blinatumomab and its activity in R/R ALL.Keywords: acute lymphoblastic leukemia, relapsed/refractory, BiTE® monoclonal antibodies, blinatumomab

  19. SET-NUP214 fusion in acute myeloid leukemia- and T-cell acute lymphoblastic leukemia-derived cell lines

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    Zaborski Margarete

    2009-01-01

    Full Text Available Abstract Background SET-NUP214 fusion resulting from a recurrent cryptic deletion, del(9(q34.11q34.13 has recently been described in T-cell acute lymphoblastic leukemia (T-ALL and in one case of acute myeloid leukemia (AML. The fusion protein appears to promote elevated expression of HOXA cluster genes in T-ALL and may contribute to the pathogenesis of the disease. We screened a panel of ALL and AML cell lines for SET-NUP214 expression to find model systems that might help to elucidate the cellular function of this fusion gene. Results Of 141 human leukemia/lymphoma cell lines tested, only the T-ALL cell line LOUCY and the AML cell line MEGAL expressed the SET(TAF-Iβ-NUP214 fusion gene transcript. RT-PCR analysis specifically recognizing the alternative first exons of the two TAF-I isoforms revealed that the cell lines also expressed TAF-Iα-NUP214 mRNA. Results of fluorescence in situ hybridization (FISH and array-based copy number analysis were both consistent with del(9(q34.11q34.13 as described. Quantitative genomic PCR also confirmed loss of genomic material between SET and NUP214 in both cell lines. Genomic sequencing localized the breakpoints of the SET gene to regions downstream of the stop codon and to NUP214 intron 17/18 in both LOUCY and MEGAL cells. Both cell lines expressed the 140 kDa SET-NUP214 fusion protein. Conclusion Cell lines LOUCY and MEGAL express the recently described SET-NUP214 fusion gene. Of special note is that the formation of the SET exon 7/NUP214 exon 18 gene transcript requires alternative splicing as the SET breakpoint is located downstream of the stop codon in exon 8. The cell lines are promising model systems for SET-NUP214 studies and should facilitate investigating cellular functions of the the SET-NUP214 protein.

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

    Science.gov (United States)

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

    2003-10-01

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

  1. MicroRNA-205 downregulates mixed-lineage-AF4 oncogene expression in acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Dou L

    2013-08-01

    Full Text Available Liping Dou,1,* Jingxin Li,1,* Dehua Zheng,2,* Yonghui Li,1 Xiaoning Gao,1 Chengwang Xu,1 Li Gao,1 Lili Wang,1 Li Yu1 1Department of Hematology, Chinese PLA General Hospital, Beijing, People's Republic of China; 2Department of Hepatobiliary Surgery, Organ Transplant Center, Chinese PLA 309th Hospital, Beijing, People's Republic of China*These authors contributed equally to this workAbstract: Myeloid/lymphoid or mixed-lineage AF4 acute lymphoblastic leukemia (MLL-AF4 ALL is a pediatric leukemia that occurs rarely in adults. MLL-AF4 ALL is typically characterized by the presence of chromosomal translocation (t(4;11(q21;q23, leading to expression of MLL-AF4 fusion protein. Although MLL-AF4 fusion protein triggers a molecular pathogenesis and hematological presentations that are unique to leukemias, the precise role of this oncogene in leukemogenesis remains unclear. Previous studies have indicated that microRNAs (miRs might modulate the expression of MLL-AF4 ALL fusion protein, thereby suggesting the involvement of miR in progression or suppression of MLL-AF4 ALL. We have previously demonstrated that miR-205 negatively regulates transcription of an MLL-AF4 luciferase reporter. Here, we report that exogenous expression of miR-205 in MLL-AF4 human cell lines (RS4;11 and MV4-11 inversely regulates the expression of MLL-AF4 at both messenger RNA (mRNA and protein level. Furthermore, miR-205 significantly induced apoptosis in MLL-AF4 cells as evidenced by Annexin V staining using fluorescence-activated cell sorting (FACS analysis. The proliferative capacity of leukemic cells was suppressed by miR-205. The addition of an miR-205 inhibitor was able to restore the observed effects. In conclusion, these findings demonstrate that miR-205 may have potential value as a novel therapeutic agent in the treatment of MLL-AF4 ALL.Keywords: miR-205, MLL-AF4, leukemia, microRNA, oncogene expression, untranslated regions, proliferation

  2. Adult acute lymphoblastic leukemia Leucemia linfoblástica do adulto

    Directory of Open Access Journals (Sweden)

    Robin Foà

    2009-08-01

    Full Text Available This review focuses on the most recent advances in the diagnostic and prognostic work-up of adult acute lymphoblastic leukemia (ALL, and on their implications in the clinical management of the disease. Over the years, information obtained through extensive immunophenotyping, karyotyping, molecular genetics, multidrug resistance and, more recently, genomic profiling is progressively contributing to a better understanding of the biology of this complex disease, to the identification of subgroups of patients with different clinical outcomes, to a more precise monitoring of minimal residual disease, to the use of different therapeutic protocols based on prognostic indicators and, finally, to the design of innovative and specific treatment strategies. The next few years will tell us if this biologically-guided approach, which is progressively individualizing the management of adult ALL patients, will ultimately impact on the prognosis of a disease that has stagnated over many decade.Esta revisão focaliza os mais recentes avanços no diagnóstico e prognóstico da leucemia linfoblástica aguda do adulto e suas implicações no manuseio clínico desta doença. Com o passar dos anos, informações obtidas através de extensa pesquisa em imunofenotipagem, citogenética, genética molecular, resistência a múltiplas drogas e, mais recentemente, perfil genômico têm contribuído progressivamente para o melhor entendimento da biologia desta doença complexa, na identificação de sub grupos de pacientes com evolução clínica distintas, no mais preciso monitoramento da doença residual mínima, no uso de diferentes protocolos baseados em indicadores prognósticos e, mais recentemente, também no desenho de tratamentos inovativos e específicos. Os próximos anos nos dirão se abordagens baseadas guiadas biologicamente, que será uma individualização progressiva do manuseio dos pacientes adultos com LLA podem causar um impacto favorável em uma doen

  3. Leucemia Linfoblástica Aguda Filadélfia positiva Phyladelphia positive acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Rony Schaffel

    2008-04-01

    Full Text Available O cromossomo Filadélfia (Ph1 é a alteração citogenética mais comum da Leucemia Linfoblástica Aguda do adulto (LLA. Esta alteração citogenética predomina nos adultos com mais de 50 anos e na LLA de origem na célula B, principalmente CD10 positiva. O diagnóstico requer a análise citogenética e a pesquisa do mRNA do gene BCR-ABL no sangue periférico ou na medula óssea. A LLA Ph1 apresenta uma sobrevida global em cinco anos inferior a 20% quando tratada com protocolos para LLA. Os poucos casos de cura ocorrem nos pacientes submetidos ao transplante alogênico de medula óssea (TMO. A adição do imatinibe à quimioterapia resultou em melhora na taxa de remissão completa, maior taxa de remissão molecular completa, maior número de pacientes aptos para realizar o TMO, uma maior sobrevida livre de eventos e maior sobrevida global, embora o tempo de seguimento seja ainda muito curto. Entretanto, a taxa de recaídas e o aparecimento de mutações do BCR-ABL resistentes ao imatinibe ainda são preocupantes. No futuro, novos inibidores de tirosina quinase poderão ser incorporados ao tratamento da LLA Ph1.The Philadelphia chromosome (Ph1 is the most frequent abnormality in acute adult lymphoblastic leukemia (ALL. Ph1 positive ALL is more frequent in over 50-year-old adults, in B-cell ALL and CD10-positive ALL. Diagnosis is based on the identification of the BCR-ABL gene mRNA in peripheral blood or bone marrow. The 5-year overall survival of patients with Ph1 positive ALL treated with chemotherapy alone is less than 20%. A few cases may be cured by allogeneic stem cell transplantation. The addition of imatinib to the chemotherapeutic treatment has resulted in more complete remissions, more complete molecular responses, more patients able to perform stem cell transplantation, better event-free survival and better overall survival, although the study follow-up period is very short so far. High relapse rates and the emergence of BCR

  4. TSER polymorphism is not associated with risk of pediatric acute lymphoblastic leukemia

    Science.gov (United States)

    Qiao, Zhaohua; Lou, Dan; Ruan, Li

    2017-01-01

    Abstract Background: Accumulating studies have explored the effect of thymidylate synthase enhancer region (TSER) variation on risk of pediatric acute lymphoblastic leukemia (ALL) with controversial results. Therefore, this quantitative meta-analysis was performed to assess synthetically the association of TSER variation with susceptibility to develop pediatric ALL. Methods: The PubMed, ScienceDirect, Google Scholar, Wanfang Database, and China National Knowledge Infrastructure were systematically retrieved to obtain the published case-control studies about the relationship between TSER variation and pediatric ALL risk. The quality assessment of the included studies was preformed and relevant information was collected. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the strength of association. Results: This meta-analysis finally included 2681 children with ALL and 3854 matched controls from 11 investigations. The quantitative synthesis results found no significant association between TSER variation and susceptibility to pediatric ALL in overall comparisons under 5 genetic models (2R/3R vs 3R/3R: OR = 0.95, 95% CI = 0.84–1.07, P = 0.41; 2R/2R vs 3R/3R: OR = 0.99, 95% CI = 0.84–1.16, P = 0.90; 2R2R vs 3R/3R+2R/3R: OR = 1.05, 95% CI = 0.92–1.21, P = 0.45; 2R/3R+2R/2R vs 3R/3R: OR = 0.97, 95% CI = 0.87–1.09, P = 0.63; 2R vs 3R: OR = 1.03, 95% CI = 0.92–1.15, P = 0.61). Similarly, there was no significant association existed in the stratification analyses according to ethnicity, control source, and quality score. Conclusion: This meta-analysis shows that TSER variation is not related to the development risk of pediatric ALL. PMID:28207544

  5. PROGNOSTIC VALUE OF PROTEASE ACTIVATED RECEPTOR-1 IN EGYPTIAN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Adel Abd Elhaleim Hagag

    2014-04-01

    Full Text Available Background: Acute Lymphoblastic leukemia (ALL is a malignant disorder of lymphoid progenitor cells that proliferate and replace the normal hematopoietic cells of the bone marrow. Protease-activated receptor 1 (PAR-1, is atypical member of this family of receptors that mediate cellular responses to thrombin and related proteases. PAR1 is expressed by a wide range of tumor cells and can promote tumor growth, invasion and metastasis. The aim of this work was to study the role of PAR-1 expression in newly diagnosed ALL patients. Patients and methods: This study was conducted on 44 children with newly diagnosed ALL who were admitted to Hematology Unit, Pediatric department, Tanta University Hospital including 24 males and 20 females with their age ranged from 4-17 years and their mean age value of 9.06±3.26 who were divided into two groups; PAR-1 positive group (18 patients and PAR-1 negative group (26 patients. All patients were subjected to complete history taking, thorough clinical examination, bone marrow aspiration and flow cytometric analysis for detection of PAR-1 expression by malignant cells. Results: PAR-1 was positive in 18 cases (41% and negative in 26 cases (59% of studied patients. This study showed no significant relation between PAR-1 expression and age, sex and most of the clinical data including hepatomegaly, splenomegaly and purpura while generalized lymphadenopathy was significantly higher in PAR-1 positive group. PAR-1 positive expression was associated with some bad prognostic laboratory parameters including higher hemoglobin, higher white blood cells, higher peripheral blood and bone marrow blast cells, higher serum LDH and lower platelets count. No significant association was detected between PAR-1 expression and immunophenotyping. There were significantly higher remission rates in PAR-1 negative group and significantly higher relapse and death rates in PAR-1 positive group. Conclusion: From this study, it could be concluded

  6. Expression of zinc finger protein X-linked in childhood B lineage acute lymphoblastic leukemia%锌指蛋白ZFX在儿童B系急性淋巴细胞性白血病中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    王卓; 梁欢欢; 李本尚; 黄小航; 张婧; 王翔; 丁丽霞; 江华

    2013-01-01

    Objective To study the expression of zinc finger protein X-linked (ZFX) in bone marrow mononuclear cells (BMMCs) of children with B lineage acute lymphoblastic leukemia (B-ALL)and its relationship with prognosis.Methods The expression of ZFX in human leukemia cell lines (REH,HL-60,NB4 and K562) was measured by Western blot.ZFX gene was cloned by PCR from one patient and DNA sequencing technology was used to confirm it.Real-time PCR was used for detecting ZFX mRNA expression in the BMMCs of 82 children with newly-diagnosed B-ALL,24 children with complete remission (CR) after induction therapy and 64 control children (fracture or congenital heart disease patients).According to the presence of bone marrow or central nervous system relapse during a follow-up of 3 years,the patients were identified as having a good or poor prognosis.Their ZFX mRNA levels in BMMCs at diagnosis were compared.Results ZFX protein was expressed in human leukemia cell lines REH,HL-60,NB4 and K562.ZFX mRNA expression was significantly higher in the newly-diagnosed ALL group than in the control group (P < 0.01).ZFX mRNA expression in the ALL CR group was significantly reduced compared with the newly-diagnosed ALL group (P < 0.01).Children with a poor prognosis had significantly higher ZFX mRNA levels at diagnosis than those with a good prognosis (P< 0.05).Conclusions ZFX is over-expressed in children with B-ALL and its levels are higher in those with a poor prognosis than those with a good prognosis,which suggests that ZFX is important in the prognosis evaluation of B-ALL.%目的 研究儿童B系急性淋巴细胞性白血病(B-ALL)患者骨髓单个核细胞中X染色体耦联锌指蛋白(ZFX)的表达及其与白血病预后的关系.方法 通过Western blot方法检测白血病细胞株(REH、HL-60、NB4、K562)中ZFX蛋白的表达;利用PCR方法扩增获得全长ZFX,并测序验证;通过实时定量PCR检测82例初发B-ALL儿童骨髓样本,24例B-ALL缓解期样本,以及64

  7. Survival in patients with acute non-lymphoblastic leukemia at the "Dr. Gustavo Aldereguía Lima". Hospital. A ten years experience

    Directory of Open Access Journals (Sweden)

    Rafael Alejandro Gómez Baute

    2010-11-01

    Full Text Available Background: acute non-lymphoblastic leukemias account for 80% of leukemias in adults. Its incidence increases with age up to 20 per 100 000 in over 70 years old patients. Objective: To characterize the survival of patients with acute non-lymphoblastic leukemia at the "Dr. Gustavo Aldereguía Lima " Hospital of Cienfuegos. Methods: A case series which included all patients who underwent diagnosis of acute non-lymphoblastic leukemia between 1999 and 2010 at the Hospital of Cienfuegos. Data were obtained from the record book of hematological malignancies from the Oncohematology Department. Such variables like age, sex, morphological variant of the leukemia, incidence per year and overall survival were analyzed according to sex, morphological variant, origin, age and bone marrow transplant. Results: The average age of the studied series was 55 years old . Males were predominant with 55 cases. The most common morphological variant was the myelomonocytic. Overall survival of the series was 20% with a median follow-up of 60 months. Overall survival was slightly higher in females (25% vs 18%. The patients who underwent some form of transplant had a better survival (75% vs 13%. Conclusions: The survival of patients with acute non-lymphoblastic leukemia at the "Dr. Aldereguía Gustavo Lima" Hospital is very limited.

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

    DEFF Research Database (Denmark)

    Ranta, Susanna; Tuckuviene, Ruta; Mäkipernaa, Anne

    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...

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  10. Resveratrol given intraperitoneally does not inhibit growth of high-risk t(4;11) acute lymphoblastic leukemia cells in NOD/SCID mouse model

    Science.gov (United States)

    The efficacy of the phytochemical resveratrol as a preventive agent against the growth of t(4;11) acute lymphoblastic leukemia (ALL) was evaluated in NOD.CB17-Prkdcscid/J mice engrafted with the human t(4;11) ALL line SEM. SEM cells were injected into the tail vein and engraftment was monitored by ...

  11. Dietary resveratrol does not delay engraftment, sensitize to vincristine, or inhibit growth of high-risk acute lymphoblastic leukemia cells in NOD/SCID mice

    Science.gov (United States)

    Acute lymphoblastic leukemia (ALL) with translocation t(4;11) is a high-risk leukemia found in 60-85% of infants with ALL and is often refractory to conventional chemotherapeutics after relapse. Although resveratrol is able to kill high-risk leukemia in vitro, this agent has not been evaluated agai...

  12. A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Seymour, J F; Kim, D W; Rubin, E;

    2014-01-01

    Aurora kinase overexpression has been observed in patients with hematologic malignancies. MK-0457, a pan-aurora kinase inhibitor that also inhibits the ABL T315I mutant, was evaluated to treat patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome (Ph+) acute lymphoblastic...

  13. Methotrexate-induced side effects are not due to differences in pharmacokinetics in children with down syndrome and acute lymphoblastic leukemia

    NARCIS (Netherlands)

    T.D. Buitenkamp (Trudy); R.A.A. Mathôt (Ron); V. de Haas (Valerie); R. Pieters (Rob); C.M. Zwaan (Christian Michel)

    2010-01-01

    textabstractBackground Children with Down syndrome have an increased risk of developing acute lymphoblastic leukemia and a poor tolerance of methotrexate. This latter problem is assumed to be caused by a higher cellular sensitivity of tissues in children with Down syndrome. However, whether differen

  14. Integrated transcript and genome analyses reveal NKX2-1 and MEF2C as potential oncogenes in T cell acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Homminga, I.; Pieters, R.; Langerak, A.W.; de Rooi, J.J.; Stubbs, A.; Verstegen, M.; Vuerhard, M.; Buijs-Gladdines, J.; Kooi, C.; Klous, P.; van Vlierberghe, P.; Ferrando, A.A.; Cayuela, J.M.; Verhaaf, B.; Beverloo, H.B.; Horstmann, M.; de Haas, V.; Wiekmeijer, A.S.; Pike-Overzet, K.; Staal, F.J.; de Laat, W.; Soulier, J.; Sigaux, F.; Meijerink, J.P.

    2011-01-01

    To identify oncogenic pathways in T cell acute lymphoblastic leukemia (T-ALL), we combined expression profiling of 117 pediatric patient samples and detailed molecular-cytogenetic analyses including the Chromosome Conformation Capture on Chip (4C) method. Two T-ALL subtypes were identified that lack

  15. Bone mineral density at diagnosis determines fracture rate in children with acute lymphoblastic leukemia treated according to the DCOG-ALL9 protocol

    NARCIS (Netherlands)

    te Winkel, Mariel L.; Pieters, Rob; Hop, Wim C. J.; Roos, Jan C.; Bokkerink, Jos P. M.; Leeuw, Jan A.; Bruin, Marrie C. A.; Kollen, Wouter J. W.; Veerman, Anjo J. P.; de Groot-Kruseman, Hester A.; van der Sluis, Inge M.; van den Heuvel-Eibrink, Marry M.

    2014-01-01

    Purpose: To elucidate incidence and risk factors of bone mineral density and fracture risk in children with Acute Lymphoblastic Leukemia (ALL). Methods: Prospectively, cumulative fracture incidence, calculated from diagnosis until one year after cessation of treatment, was assessed in 672 patients.

  16. Bone mineral density at diagnosis determines fracture rate in children with acute lymphoblastic leukemia treated according to the DCOG-ALL9 protocol

    NARCIS (Netherlands)

    Winkel, M.L. te; Pieters, R.; Hop, W.C.J.; Roos, J.C.; Bokkerink, J.P.M.; Leeuw, J.A. de; Bruin, M.C.; Kollen, W.J.; Veerman, A.J.P.; Groot-Kruseman, H.A. de; Sluis, I.M. van der; Heuvel-Eibrink, M.M. van den

    2014-01-01

    PURPOSE: To elucidate incidence and risk factors of bone mineral density and fracture risk in children with Acute Lymphoblastic Leukemia (ALL). METHODS: Prospectively, cumulative fracture incidence, calculated from diagnosis until one year after cessation of treatment, was assessed in 672 patients.

  17. Acute lymphoblastic leukaemia after treatment of nephrotic syndrome with immunosuppressive drugs.

    Science.gov (United States)

    Kuis, W; de Kraker, J; Kuijten, R H; Donckerwolcke, R A; Voûte, P A

    1976-06-01

    The authors present a 4-year-old girl with nephrotic syndrome who developed actue lymphoblastic leukaemia 5 months after the start of a combined treatment of alternate day prednisone and daily cyclophosphamide during 3 months. The nephrotic syndrome was due to focal segmental glomerulosclerosis. The occurrence of leukaemia might be related to the preceeding treatment with cyclophosphamide.

  18. Fatal Ophiostoma piceae infection in a patient with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Bommer, M.; Hütter, M.L.; Stilgenbauer, S.; de Hoog, G.S.; de Beer, Z.W.; Wellinghausen, N.

    2009-01-01

    We report to our knowledge the first case of human infection with Ophiostoma piceae. This Sporothrix schenckii-related fungus caused disseminated infection involving the lung and the brain in a patient with lymphoblastic lymphoma. The case emphasizes the significance of molecular techniques for iden

  19. Fatal Ophiostoma piceae infection in a patient with acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Bommer, M.; Hutter, M.L.; Stilgenbauer, S.; de Hoog, G.S.; de Beer, Z.W.; Wellinghausen, N.

    2009-01-01

    We report to our knowledge the first case of human infection with Ophiostoma piceae. This Sporothrix schenckii-related fungus caused disseminated infection involving the lung and the brain in a patient with lymphoblastic lymphoma. The case emphasizes the significance of molecular techniques for iden

  20. Aurora kinases in childhood acute leukemia: The promise of aurora B as therapeutic target

    NARCIS (Netherlands)

    S.A. Hartsink-Segers (S.); C.M. Zwaan (Michel); C. Exalto (Carla); M.W.J. Luijendijk (M. W J); V. Calvert (V.); E.F. Petricoin (Emanuel F.); W.E. Evans (William); D. Reinhardt (Dirk); V. de Haas (Valerie); M. Hedtjärn (M.); B.R. Hansen (B.); T. Koch (T.); H.N. Caron (Huib); R. Pieters (Rob); M.L. den Boer (Monique)

    2013-01-01

    textabstractWe investigated the effects of targeting the mitotic regulators aurora kinase A and B in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Aurora protein expression levels in pediatric ALL and AML patient samples were determined by western blot and reverse ph