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Sample records for acute lymphoblastic leukemias

  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...... determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic polymorphisms have been recognized that show susceptibility to developing ALL and that help explain the racial/ethnic differences in the incidence of ALL. CONCLUSION: The information gained...

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

    Science.gov (United States)

    2017-02-13

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

  3. Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)

    Science.gov (United States)

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

  4. Stages of Adult Acute Lymphoblastic Leukemia

    Science.gov (United States)

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

  5. Treatment Options for Adult Acute Lymphoblastic Leukemia

    Science.gov (United States)

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

  6. General Information about Adult Acute Lymphoblastic Leukemia

    Science.gov (United States)

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

  7. Acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Robin Foà

    2011-06-01

    Full Text Available Acute lymphoblastic leukemia (ALL is the most frequent neoplasm in children, while being relatively rare in adults. The outcome of children with ALL is far superior than that observed in adults, whose survival rates generally do not exceed 40%. A retrospective analysis recently carried out on a large series of cases enrolled in the AIEOP and GIMEMA protocols for the treatment of pediatric and adult ALL has documented specific differences among the various age cohorts examined, particularly in terms of incidence of molecular rearrangements, with the BCR/ABL rearrangement being detected in more than half of patients in the 6th decade of life. These findings highlight the importance of a precise diagnostic screening at all ages, since elderly patients might benefit more from targeted approaches, that are associated with less toxic effects. Furthermore, extended biologic approaches aimed at identifying novel therapeutic targets should be regarded as a main goal to refine our therapeutic armamentarium. Finally, the introduction of pediatric-like protocols is progressively changing the outcome of young adult patients, although an important caveat is represented by the comorbidities and toxic effects associated with more aggressive chemotherapy; therefore, patients’ fitness should always be carefully considered.

  8. 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

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

    Science.gov (United States)

    ... the Flu Vaccine? Eating Disorders Arrhythmias Acute Lymphoblastic Leukemia (ALL) KidsHealth > For Parents > Acute Lymphoblastic Leukemia (ALL) ... Treatment Coping en español Leucemia linfoblástica aguda About Leukemia Leukemia is a type of cancer that affects ...

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

    Science.gov (United States)

    2013-10-07

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

  11. Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations

    Science.gov (United States)

    2018-02-02

    B Acute Lymphoblastic Leukemia; Central Nervous System Leukemia; Ph-Like Acute Lymphoblastic Leukemia; Testicular Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  12. 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...

  13. Risk Groups for Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... for cancer and certain genetic conditions affect the risk of having childhood ALL. Anything that increases your ... marrow or in other parts of the body. Risk Groups for Childhood Acute Lymphoblastic Leukemia Key Points ...

  14. ALL (Acute Lymphoblastic Leukemia) Guide: Information for Patients and Caregivers

    Science.gov (United States)

    The ALL Guide Information for Patients and Caregivers Acute Lymphoblastic Leukemia This publication was sponsored by Estephana , ALL survivor ... day most people who have been diagnosed with acute lymphoblastic leukemia (ALL) will be cured or they will be ...

  15. CD19/CD22 Chimeric Antigen Receptor T Cells and Chemotherapy in Treating Children or Young Adults With Recurrent or Refractory CD19 Positive B Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2017-11-20

    B Acute Lymphoblastic Leukemia; CD19 Positive; Minimal Residual Disease; Philadelphia Chromosome Positive; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Refractory Acute Lymphoblastic Leukemia

  16. Cardiac Manifestation of Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Werner, Rudolf A; Rudelius, Martina; Thurner, Annette; Higuchi, Takahiro; Lapa, Constantin

    2016-07-01

    Here, we report on a 38-year-old man with unclear right heart failure. Imaging with cardiac MRI and combined PET/CT with F-FDG revealed a hypermetabolic mass extending from the right ventricle to the atrium. In addition, intense glucose utilization throughout the bone marrow was noted. Biopsies of both bone marrow and cardiac mass were performed and revealed precursor B-cell acute lymphoblastic leukemia with gross leukemic infiltration of the myopericardium, a rare manifestation of acute lymphoblastic leukemia at initial diagnosis.

  17. MANAGEMENT OF PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    A. S. Falade

    2017-06-01

    Full Text Available The lecture presents modern data on acute lymphoblastic leukemia as the one of the most common malignant disease of children, youth and the elderly. The data on the major risk factors, causes, pathogenesis, clinical manifestations, as well as the main approaches to the diagnosis and treatment of this disease and possible predictions for patients in different clinical situations are described.

  18. Flavopiridol in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

    Science.gov (United States)

    2013-06-03

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia

  19. Motor performance of children during treatment for acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Reinders-Messelink, H.; Schoemaker, M.; Snijders, T.; Göeken, L.N.; van de Briel, M.; Bokkerink, J.; Kamps, W.

    1999-01-01

    Background. Daily life motor skills of children with acute lymphoblastic leukemia (ALL) were studied during treatment using the Movement Assessment Battery for Children (Movement ABC). In addition, the possible relation with vincristine treatment was investigated. Procedure. Seventeen children

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

    Science.gov (United States)

    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

  1. Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Baytan, Birol; Evim, Melike Sezgin; Güler, Salih; Güneş, Adalet Meral; Okan, Mehmet

    2015-10-01

    The outcome of childhood acute lymphoblastic leukemia has improved because of intensive chemotherapy and supportive care. The frequency of adverse events has also increased, but the data related to acute central nervous system complications during acute lymphoblastic leukemia treatment are sparse. The purpose of this study is to evaluate these complications and to determine their long term outcome. We retrospectively analyzed the hospital reports of 323 children with de novo acute lymphoblastic leukemia from a 13-year period for acute neurological complications. The central nervous system complications of leukemic involvement, peripheral neuropathy, and post-treatment late-onset encephalopathy, and neurocognitive defects were excluded. Twenty-three of 323 children (7.1%) suffered from central nervous system complications during acute lymphoblastic leukemia treatment. The majority of these complications (n = 13/23; 56.5%) developed during the induction period. The complications included posterior reversible encephalopathy (n = 6), fungal abscess (n = 5), cerebrovascular lesions (n = 5), syndrome of inappropriate secretion of antidiuretic hormone (n = 4), and methotrexate encephalopathy (n = 3). Three of these 23 children (13%) died of central nervous system complications, one from an intracranial fungal abscess and the others from intracranial thrombosis. Seven of the survivors (n = 7/20; 35%) became epileptic and three of them had also developed mental and motor retardation. Acute central neurological complications are varied and require an urgent approach for proper diagnosis and treatment. Collaboration among the hematologist, radiologist, neurologist, microbiologist, and neurosurgeon is essential to prevent fatal outcome and serious morbidity. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Eliminating acute lymphoblastic leukemia cells from human testicular cell cultures: a pilot study

    NARCIS (Netherlands)

    Sadri-Ardekani, Hooman; Homburg, Christa H.; van Capel, Toni M. M.; van den Berg, Henk; van der Veen, Fulco; van der Schoot, C. Ellen; van Pelt, Ans M. M.; Repping, Sjoerd

    2014-01-01

    To study whether acute lymphoblastic leukemia (ALL) cells survive in a human testicular cell culture system. Experimental laboratory study. Reproductive biology laboratory, academic medical center. Acute lymphoblastic leukemia cells from three patients and testicular cells from three other patients.

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

    OpenAIRE

    Degryse, Sandrine; Cools, Jan

    2015-01-01

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

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

    Science.gov (United States)

    Degryse, Sandrine; Cools, Jan

    2015-07-26

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

  5. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration

    Science.gov (United States)

    Yang, Jun J.; Hunger, Stephen P.; Pieters, Rob; Schrappe, Martin; Biondi, Andrea; Vora, Ajay; Baruchel, André; Silverman, Lewis B.; Schmiegelow, Kjeld; Escherich, Gabriele; Horibe, Keizo; Benoit, Yves C.M.; Izraeli, Shai; Yeoh, Allen Eng Juh; Liang, Der-Cherng; Downing, James R.; Evans, William E.; Relling, Mary V.; Mullighan, Charles G.

    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 reviewed and revised by the committee chairs of the major ALL study groups. Results With long-term survival rates for ALL approaching 90% and the advent of high-resolution genome-wide analyses, several international study groups or consortia were established to conduct collaborative research to further improve outcome. As a result, treatment strategies have been improved for several subtypes of ALL, such as infant, MLL-rearranged, Philadelphia chromosome–positive, and Philadelphia chromosome–like ALL. Many recurrent genetic abnormalities that respond to tyrosine kinase inhibitors and multiple genetic determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic polymorphisms have been recognized that show susceptibility to developing ALL and that help explain the racial/ethnic differences in the incidence of ALL. Conclusion The information gained from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL. PMID:26304874

  6. [Acute lymphoblastic leukemia: a genomic perspective].

    Science.gov (United States)

    Jiménez-Morales, Silvia; Hidalgo-Miranda, Alfredo; Ramírez-Bello, Julián

    In parallel to the human genome sequencing project, several technological platforms have been developed that let us gain insight into the genome structure of human entities, as well as evaluate their usefulness in the clinical approach of the patient. Thus, in acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, genomic tools promise to be useful to detect patients at high risk of relapse, either at diagnosis or during treatment (minimal residual disease), and they also increase the possibility to identify cases at risk of adverse reactions to chemotherapy. Therefore, the physician could offer patient-tailored therapeutic schemes. A clear example of the useful genomic tools is the identification of single nucleotide polymorphisms (SNPs) in the thiopurine methyl transferase (TPMT) gene, where the presence of two null alleles (homozygous or compound heterozygous) indicates the need to reduce the dose of mercaptopurine by up to 90% to avoid toxic effects which could lead to the death of the patient. In this review, we provide an overview of the genomic perspective of ALL, describing some strategies that contribute to the identification of biomarkers with potential clinical application. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  7. [Epigenetic alterations in acute lymphoblastic leukemia].

    Science.gov (United States)

    Navarrete-Meneses, María Del Pilar; Pérez-Vera, Patricia

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. It is well-known that genetic alterations constitute the basis for the etiology of ALL. However, genetic abnormalities are not enough for the complete development of the disease, and additional alterations such as epigenetic modifications are required. Such alterations, like DNA methylation, histone modifications, and noncoding RNA regulation have been identified in ALL. DNA hypermethylation in promoter regions is one of the most frequent epigenetic modifications observed in ALL. This modification frequently leads to gene silencing in tumor suppressor genes, and in consequence, contributes to leukemogenesis. Alterations in histone remodeling proteins have also been detected in ALL, such as the overexpression of histone deacetylases enzymes, and alteration of acetyltransferases and methyltransferases. ALL also shows alteration in the expression of miRNAs, and in consequence, the modification in the expression of their target genes. All of these epigenetic modifications are key events in the malignant transformation since they lead to the deregulation of oncogenes as BLK, WNT5B and WISP1, and tumor suppressors such as FHIT, CDKN2A, CDKN2B, and TP53, which alter fundamental cellular processes and potentially lead to the development of ALL. Both genetic and epigenetic alterations contribute to the development and evolution of ALL. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  8. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    DEFF Research Database (Denmark)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

    2016-01-01

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

  9. Bilateral proliferative retinopathy in B-cell acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Devesh Kumawat

    2018-01-01

    Full Text Available A 4-year-old child with B-cell acute lymphoblastic leukemia presented with vitreous hemorrhage due to proliferative retinopathy in both eyes. Pars plana vitrectomy was performed in both eyes to clear nonresolving vitreous hemorrhage after systemic stabilization. Visual recovery was limited by the disc drag in the right eye and subfoveal exudation in the left eye. Etiopathogenesis and management of proliferative retinopathy in acute leukemias are discussed.

  10. ACUTE LYMPHOBLASTIC LEUKEMIA WITHOUT CIRCULATING BLASTS PRESENTING AS SEVERE HYPERCALCEMIA

    Directory of Open Access Journals (Sweden)

    Z. Oloomi

    2007-05-01

    Full Text Available Hypercalcemia complicating malignancy is a rare complication in pediatric age group. In this article, we present a case with acute lymphoblastic leukemia presenting as severe hypercalcemia. A 10 years old girl presented with an acute onset of fever, nausea, vomiting, loss of weight, costovertebral pain and frequency. She was admitted with a presumptive diagnosis of acute pyelonephritis. Her examination showed mild hepatosplenomegaly. In laboratory studies she had sever hypercalcemia. Despite the absence of circulating blast, bone marrow aspiration was diagnostic of acute lymphoblastic leukemia. The hypercalcemia was initially treated with intravenous hydration and furosemide but the serum calcium levels normalized only after the beginning of specific chemotherapy. Hypercalcemia represents an emergency in children, and acute leukemia must be considered in differential diagnosis even when there are no circulating blasts.

  11. 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...

  12. 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...

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

    Science.gov (United States)

    Janzen, Laura A.; Spiegler, Brenda J.

    2008-01-01

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

  14. 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...

  15. Terson Syndrome Before Induction Chemotherapy for Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Wang, YunZu Michele; Nudleman, Eric; Vinocur, Daniel; Kuo, Dennis John

    2017-12-01

    A previously healthy 2-year-old female infant presented with pancytopenia and was diagnosed with acute lymphoblastic leukemia. Before the initiation of treatment, she developed symptoms concerning for increased intracranial pressure. Head imaging revealed left parietal hemorrhage, in addition to a right vitreous hemorrhage, which was confirmed on ophthalmology examination later. Terson syndrome, in which intraocular hemorrhage is associated with intracranial hemorrhage, is more commonly reported in adults, although ocular manifestations of leukemia have been reported at presentation and are typically asymptomatic.

  16. 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.

  17. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Müller, Klaus Gottlob; Mogensen, Signe Sloth

    2017-01-01

    During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal...... useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall...

  18. IMMUNOLOGICAL CLASSIFICATION OF ACUTE LYMPHOBLASTIC LEUKEMIAS

    Directory of Open Access Journals (Sweden)

    Samo Zver

    2002-05-01

    Full Text Available Background. ALL is a malignant blood disease and lymphoblasts have origin in B or T lymphatic cell line. In 1997 established new World Health Organisation classification (WHO classification of malignant haematological diseases realizes the importance of cellular immunological markers (immunophenotype and chromosomal abnormalities (cytogenetics. Based on both findings we may distribute the patients in low, intermediate and high risk groups and the outcome of such distribution is risk adopted ALL treatment strategy. On Clinical department of haematology (CDH we have decided to overview immunophenotype characteristics of all ALL patients during the January 1, 1995–December 31, 2001 period.Methods and results. During the January 1, 1995–December 31, 2001 period on CDH we have treated 44 patients: 22 males and 22 females. With flow cytometer Coulter Epics XL MCS we have performed first primary antibody panel for acute leukemias antigens (CD2, CD7, CD10, CD19, CD34, cCD3, cCD13, cCD22, MPO, TdT, followed by secondary panel. The later have included antigen CD20, CD23, membrane and/or cytoplasmatic immunoglobulins or their light chains monoclonal antibodies for B-ALL and antigen CD3, CD4, CD5 and CD8 monoclonal antibodies for T-ALL subsets. Besides immunophenotyping we have evaluated all ALL patients also morphologically according to FAB classification (French-AmericanBritish classification, which is an old classification based solely on morphology.32/44 (73% patients have had immunophenotypic B-ALL, and 12/44 (27% T-ALL. Subgroups distribution of B-ALL immunophenotype were: pro-B 4/44 (9%, »common«-B 18/44 (41%, pre-B 5/44 (11.5% and mature B 5744 (11.5% and for T-ALL immunophenotype were: pro-T 2/44 (4.5%, pre-T 5/44 (11.5%, cortical-T 4/44 (9% and mature-T 1/44 (2%. Our results are quite comparable with the available data from the literature, despite the fact that newest immunological markers such as CD1a, CD79a and CD22 were not available

  19. Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes

    Science.gov (United States)

    2017-10-24

    Acute Biphenotypic Leukemia; Acute Erythroid Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Blasts Under 10 Percent of Bone Marrow Nucleated Cells; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Pancytopenia; Refractory Anemia; Secondary Acute Myeloid Leukemia

  20. 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...

  1. Fatal Candidemia in a Patient with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2018-02-16

    REPORT TYPE 3. DATESCOVERED,rom-To) 02/16(2018 Abstract 02/16/201 02/20/20ISl 4. TITLE AND SUBTITLE "· CONTRACT NUMBER fatal Candiden1ia in a Patient...NOTES 14. ABSTRACT Fatal Candidcn1ia in a Patient \\\\ith Acute Lympboblastic Leukemia Brittany Lenz. MD. Arturo Dominguez.. MD. Adnan J’vlir. MD, PhD...Profoosionaf 7 ,0 Fatal Candidemia in a Patient with Acute Lymphoblastic Leukemia Brittany Lenz, MD, Arturo Dominguez, MD, Adnan Mir, MD, PhD Objectives

  2. Esophageal strictures during treatment for acute lymphoblastic leukemia.

    Science.gov (United States)

    Kelly, Kevin; Storey, Lorna; O' Sullivan, Maureen; Butler, Karina; McDermott, Michael; Corbally, Martin; McMahon, Corrina; Smith, Owen P; O' Marcaigh, Aengus

    2010-03-01

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

  3. 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.

  4. 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

  5. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    DEFF Research Database (Denmark)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

    2016-01-01

    leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were......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...

  6. New decision support tool for acute lymphoblastic leukemia classification

    Science.gov (United States)

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

    2012-03-01

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

  7. Early presentation of osteonecrosis in acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Mogensen, Signe Sloth; Harila-Saari, Arja; Frandsen, Thomas Leth

    2017-01-01

    Osteonecrosis (ON) is usually considered treatment related in patients with acute lymphoblastic leukemia (ALL). We report two patients with presentation of ON at the time of ALL diagnosis. Both were females and diagnosed with ALL at age 8 and 14 years. In the latter, some symptoms and radiologica...... and radiologically verified ON in both knees were still present after the end of ALL therapy. No pediatric patients have previously been reported with ON presenting before initiation of ALL therapy.......Osteonecrosis (ON) is usually considered treatment related in patients with acute lymphoblastic leukemia (ALL). We report two patients with presentation of ON at the time of ALL diagnosis. Both were females and diagnosed with ALL at age 8 and 14 years. In the latter, some symptoms...

  8. Compliance with a protocol for acute lymphoblastic leukemia in childhood

    Directory of Open Access Journals (Sweden)

    Benigna Maria de Oliveira

    2011-06-01

    Full Text Available BACKGROUND: Remission rates achieved after the initial treatment of acute lymphoblastic leukemia may be similar in both developed and developing countries, but relapse rates are much higher in the latter. Thus, other reasons are needed, in addition to biological characteristics of the leukemic cells themselves, to explain the unfavorable evolution of patients living in unfavorable socioeconomic and cultural conditions. OBJECTIVE: The aim of this study was to retrospectively evaluate compliance to an acute lymphoblastic leukemia treatment protocol. METHODS: Main abstracted data were: total duration and reasons for interruption of chemotherapy, prescribed doses of 6-mercaptopurine, and median white blood cell and neutrophil counts during the maintenance phase. Interruptions of chemotherapy were considered inappropriate if they did not follow predetermined criteria established in the protocol. RESULTS: Fourteen of 73 patients (19.2% unduly interrupted chemotherapy by determination of their physicians. The median white blood cell count was higher when compared with the protocol recommendations; the median 6-MP dose was lower than the standard recommended dose. The estimated probability of event-free survival was higher for patients with lower median leukocyte counts and close to those predetermined by the protocol. Event-free survival was also higher for children with a higher percentage of days without chemotherapy due to bone marrow or liver toxicity excluding undue interruptions. In multivariate analysis, both factors remained statistically significant. These results suggest that the intensity of maintenance chemotherapy may not have been enough in some children, to achieve adequate myelosuppression, hence the observation of higher leukocyte counts and none or rare episodes of therapy interruption. CONCLUSIONS: Compliance to the therapeutic protocol by both doctors and patients should always be considered in the evaluation of therapeutic failure

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-08-01

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

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

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    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.

  11. Liver transplantation in an adolescent with acute liver failure from acute lymphoblastic leukemia.

    Science.gov (United States)

    Reddi, D M; Barbas, A S; Castleberry, A W; Rege, A S; Vikraman, D S; Brennan, T V; Ravindra, K V; Collins, B H; Sudan, D L; Lagoo, A S; Martin, A E

    2014-03-01

    The most common identifiable causes of acute liver failure in pediatric patients are infection, drug toxicity, metabolic disease, and autoimmune processes. In many cases, the etiology of acute liver failure cannot be determined. Acute leukemia is an extremely rare cause of acute liver failure, and liver transplantation has traditionally been contraindicated in this setting. We report a case of acute liver failure in a previously healthy 15-yr-old male from pre-B-cell acute lymphoblastic leukemia. He underwent liver transplantation before the diagnosis was established, and has subsequently received chemotherapy for pre-B-cell acute lymphoblastic leukemia. He is currently alive 31 months post-transplantation. The published literature describing acute lymphoblastic leukemia as a cause of acute liver failure is reviewed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. 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...

  13. 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.

  14. [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.

  15. Treatment Options for Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  16. Treatment Option Overview (Childhood Acute Lymphoblastic Leukemia)

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  17. Aberrant Signaling Pathways in T-Cell Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Bongiovanni, Deborah; Saccomani, Valentina

    2017-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease caused by the malignant transformation of immature progenitors primed towards T-cell development. Clinically, T-ALL patients present with diffuse infiltration of the bone marrow by immature T-cell blasts high blood cell counts, mediastinal involvement, and diffusion to the central nervous system. In the past decade, the genomic landscape of T-ALL has been the target of intense research. The identification of specific genomic alterations has contributed to identify strong oncogenic drivers and signaling pathways regulating leukemia growth. Notwithstanding, T-ALL patients are still treated with high-dose multiagent chemotherapy, potentially exposing these patients to considerable acute and long-term side effects. This review summarizes recent advances in our understanding of the signaling pathways relevant for the pathogenesis of T-ALL and the opportunities offered for targeted therapy. PMID:28872614

  18. Acute lymphoblastic leukemia: a comprehensive review and 2017 update

    Science.gov (United States)

    Terwilliger, T; Abdul-Hay, M

    2017-01-01

    Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States alone. The hallmark of ALL is chromosomal abnormalities and genetic alterations involved in differentiation and proliferation of lymphoid precursor cells. In adults, 75% of cases develop from precursors of the B-cell lineage, with the remainder of cases consisting of malignant T-cell precursors. Traditionally, risk stratification has been based on clinical factors such age, white blood cell count and response to chemotherapy; however, the identification of recurrent genetic alterations has helped refine individual prognosis and guide management. Despite advances in management, the backbone of therapy remains multi-agent chemotherapy with vincristine, corticosteroids and an anthracycline with allogeneic stem cell transplantation for eligible candidates. Elderly patients are often unable to tolerate such regimens and carry a particularly poor prognosis. Here, we review the major recent advances in the treatment of ALL. PMID:28665419

  19. Pyomyositis During Induction Chemotherapy for Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Kai-Liang Kao

    2006-04-01

    Full Text Available Herein, we report on the correct diagnosis and effective treatment procedures for pyomyositis, a very rare complication that remains a diagnostic challenge in children being treated for acute lymphoblastic leukemia (ALL. We report the case of a 10-year-old girl suffering from pyomyositis with ALL. Correct diagnosis is usually delayed because the initial symptom of pyomyositis, usually local pain, is similar to the common side effect of vincristine, a drug necessary for ALL induction therapy. We summarize the procedures taken to reach a timely diagnosis and therapeutic success.

  20. Cytogenetic Instability in Childhood Acute Lymphoblastic Leukemia Survivors

    Directory of Open Access Journals (Sweden)

    María Sol Brassesco

    2011-01-01

    Full Text Available Contemporary anticancer therapies have largely improved the outcome for children with cancer, especially for Acute Lymphoblastic Leukemia (ALL. Actually, between 78% and 85% of patients achieve complete remission and are alive after 5 years of therapy completion. However, as cure rates increase, new concerns about the late effects of genotoxic treatment emerge, being the risk of developing secondary neoplasias, the most serious life-threatening rising problem. In the present paper, we describe and review the cytogenetic findings in peripheral lymphocytes from ALL survivors, and discuss aspects associated to the occurrence of increased chromosome rearrangements in this growing cohort.

  1. Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Acute Leukemia

    Science.gov (United States)

    2013-10-07

    Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. Association of ARID5B gene variants with acute lymphoblastic leukemia in Yemeni children.

    Science.gov (United States)

    Al-Absi, Boshra; Noor, Suzita M; Saif-Ali, Riyadh; Salem, Sameer D; Ahmed, Radwan H; Razif, Muhammad Fm; Muniandy, Sekaran

    2017-04-01

    Studies have shown an association between ARID5B gene polymorphisms and childhood acute lymphoblastic leukemia. However, the association between ARID5B variants and acute lymphoblastic leukemia among the Arab population still needs to be studied. The aim of this study was to investigate the association between ARID5B variants with acute lymphoblastic leukemia in Yemeni children. A total of 14 ARID5B gene single nucleotide polymorphisms (SNPs) were genotyped in 289 Yemeni children, of whom 136 had acute lymphoblastic leukemia and 153 were controls, using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Using logistic regression adjusted for age and gender, the risks of acute lymphoblastic leukemia were presented as odds ratios and 95% confidence intervals. We found that nine SNPs were associated with acute lymphoblastic leukemia under additive genetic models: rs7073837, rs10740055, rs7089424, rs10821936, rs4506592, rs10994982, rs7896246, rs10821938, and rs7923074. Furthermore, the recessive models revealed that six SNPs were risk factors for acute lymphoblastic leukemia: rs10740055, rs7089424, rs10994982, rs7896246, rs10821938, and rs7923074. The gender-specific impact of these SNPs under the recessive genetic model revealed that SNPs rs10740055, rs10994982, and rs6479779 in females, and rs10821938 and rs7923074 in males were significantly associated with acute lymphoblastic leukemia risk. Under the dominant model, SNPs rs7073837, rs10821936, rs7896246, and rs6479778 in males only showed striking association with acute lymphoblastic leukemia. The additive model revealed that SNPs with significant association with acute lymphoblastic leukemia were rs10821936 (both males and females); rs7073837, rs10740055, rs10994982, and rs4948487 (females only); and rs7089424, rs7896246, rs10821938, and rs7923074 (males only). In addition, the ARID5B haplotype block (CGAACACAA) showed a higher risk for acute lymphoblastic leukemia. The haplotype (CCCGACTGC) was

  3. Fulminant Aeromonas hydrophila infection during acute lymphoblastic leukemia treatment.

    Science.gov (United States)

    Papadakis, Vassilios; Poniros, Nikolaos; Katsibardi, Karerina; Charissiadou, Athina-Eleni; Anastasopoulos, John; Polychronopoulou, Sophia

    2012-04-01

    Aeromonas hydrophila septicemia has a fulminant course and it has been usually reported in immunocompromised hosts and rarely among children with leukemia. High morbidity and mortality is associated with A hydrophila infections. We describe the case of a child with acute lymphoblastic leukemia who presented with septicemia due to A hydrophila. The patient presented with fever and skin discoloration during a febrile neutropenia episode, which rapidly evolved into bacteremia and extensive thigh suppuration, fasciitis, and myonecrosis. Apart from antibiotic treatment, surgical debridement to relieve compartment pressure and prevent further lower extremity compromise was promptly performed. Despite long delays in chemotherapy and an extensive tissue gap, primary closure of the involved area was possible with full cosmetic and functional limb recovery, and the patient has remained in clinical remission for more than 7 years. Copyright © 2011. Published by Elsevier B.V.

  4. Acute renal failure as an initial manifestation of acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    N G Bhatia

    2013-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is the most common malignancy in children. Acute renal failure is a well-recognized complication of ALL after initiation of chemotherapy. Renal failure as the primary manifestation of ALL is rare. Here, we report three children who presented with acute renal failure and hyperuricemia and were subsequently diagnosed to have ALL.

  5. Acute renal failure as an initial manifestation of acute lymphoblastic leukemia

    OpenAIRE

    Bhatia, N. G.; Sneha, L. M.; Selvan, S. M.; Scott, J. J. X.

    2013-01-01

    Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Acute renal failure is a well-recognized complication of ALL after initiation of chemotherapy. Renal failure as the primary manifestation of ALL is rare. Here, we report three children who presented with acute renal failure and hyperuricemia and were subsequently diagnosed to have ALL.

  6. Acute renal failure as an initial manifestation of acute lymphoblastic leukemia.

    Science.gov (United States)

    Bhatia, N G; Sneha, L M; Selvan, S M; Scott, J J X

    2013-07-01

    Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Acute renal failure is a well-recognized complication of ALL after initiation of chemotherapy. Renal failure as the primary manifestation of ALL is rare. Here, we report three children who presented with acute renal failure and hyperuricemia and were subsequently diagnosed to have ALL.

  7. Treatment of Acute Lymphoblastic Leukemia from Traditional Chinese Medicine

    Directory of Open Access Journals (Sweden)

    Ya-Li Hsiao

    2014-01-01

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

  8. Targeting signaling pathways in acute lymphoblastic leukemia: new insights.

    Science.gov (United States)

    Harrison, Christine J

    2013-01-01

    The genetics of acute lymphoblastic leukemia are becoming well understood and the incidence of individual chromosomal abnormalities varies considerably with age. Cytogenetics provide reliable risk stratification for treatment: high hyperdiploidy and ETV6-RUNX1 are good risk, whereas BCR-ABL1, MLL rearrangements, and hypodiploidy are poor risk. Nevertheless, some patients within the good- and intermediate-risk groups will unpredictably relapse. With advancing technologies in array-based approaches (single nucleotide polymorphism arrays) and next-generation sequencing to study the genome, increasing numbers of new genetic changes are being discovered. These include deletions of B-cell differentiation and cell cycle control genes, as well as mutations of genes in key signaling pathways. Their associations and interactions with established cytogenetic subgroups and with each other are becoming elucidated. Whether they have a link to outcome is the most important factor for refinement of risk factors in relation to clinical trials. For several newly identified abnormalities, including intrachromosomal amplification of chromosome 21 (iAMP21), that are associated with a poor prognosis with standard therapy, appropriately modified treatment has significantly improved outcome. After the successful use of tyrosine kinase inhibitors in the treatment of BCR-ABL1-positive acute lymphoblastic leukemia, patients with alternative ABL1 translocations and rearrangements involving PDGFRB may benefit from treatment with tyrosine kinase inhibitors. Other aberrations, for example, CRLF2 overexpression and JAK2 mutations, are also providing potential novel therapeutic targets with the prospect of reduced toxicity.

  9. 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.

  10. 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

    2017-02-01

    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 central

  11. 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.

  12. Expression of HER2/Neu in B-Cell Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Rodriguez-Rodriguez, Sergio; Pomerantz, Alan; Demichelis-Gomez, Roberta; Barrera-Lumbreras, Georgina; Barrales-Benitez, Olga; Aguayo-Gonzalez, Alvaro

    2016-01-01

    The expression of HER2/neu in B-cell acute lymphoblastic leukemia has been reported in previous studies. The objective of this research was to study the expression of HER2/neu on the blasts of patients with acute leukemia from the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. From June 2015 to February 2016, a HER2/neu monoclonal antibody was added to the panel of antibodies that we routinely use in patients with acute leukemia. An expression of ≥ 30% was considered positive. We studied 33 patients: 19 had de novo leukemia (57.6%), three (9.1%) were in relapse, and in 11 (33.3%) their status could not be specified. Seventeen patients (51.5%) were classified as B-cell acute lymphoblastic leukemia with a median expression of HER2/neu of 0.3% (range 0-90.2). Three patients with B-cell acute lymphoblastic leukemia were positive for HER2/neu: 89.4%, 90.9%, and 62.4%. The first and third patient had de novo B-cell acute lymphoblastic leukemia. The second patient was in second relapse after allogeneic stem cell transplant. All three patients were categorized as high-risk at the time of diagnosis. In the studied Mexican population, we found a positive expression of HER2/neu in 17% of the B-cell acute lymphoblastic leukemia patients, similar to previous studies in which the expression was found in 15-50%.

  13. Individualized 6-mercaptopurine increments in consolidation treatment of childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Tulstrup, Morten; Frandsen, Thomas L; Abrahamsson, Jonas

    2018-01-01

    OBJECTIVES: This randomized controlled trial tested the hypothesis that children with non-high-risk acute lymphoblastic leukemia could benefit from individualized 6-mercaptopurine increments during consolidation therapy (NCT00816049). Primary and secondary end points were end of consolidation...

  14. Predicting the neurobehavioral side effects of dexamethasone in pediatric acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Warris, Lidewij T.; van den Akker, Erica L. T.; Aarsen, Femke K.; Bierings, Marc B.; van den Bos, Cor; Tissing, Wim J. E.; Sassen, Sebastiaan D. T.; Veening, Margreet A.; Zwaan, Christian M.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2016-01-01

    Although dexamethasone is an effective treatment for acute lymphoblastic leukemia (ALL), it can induce a variety of serious neurobehavioral side effects. We hypothesized that these side effects are influenced by glucocorticoid sensitivity at the tissue level. We therefore prospectively studied

  15. 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

  16. Resistance to different classes of drugs is associated with impaired apoptosis in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    A. Holleman (Amy); M.L. den Boer (Monique); K.M. Kazemier (Karin); G.E. Janka-Schaub (Gritta); R. Pieters (Rob)

    2003-01-01

    textabstractResistance of leukemic cells to chemotherapeutic agents is associated with an unfavorable outcome in pediatric acute lymphoblastic leukemia (ALL). To investigate the underlying mechanisms of cellular drug resistance, the activation of various apoptotic parameters in

  17. Clinical features and survival pattern of central nervous system leukemia in children with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Hardiono D. Pusponegoro

    2006-10-01

    Full Text Available Infiltration of leukemic cells into the central nervous system (CNS is one of the causes of neurological disorders in patients with acute lymphoblastic leukemia (ALL that worsen the prognosis. This retrospective cohort study aimed to review the clinical manifestations of children with CNS leukemia, their survival pattern and the role of early CNS leukemial. The survival curve was developed by Kaplan-Meier method, while the comparison of survival curves was done with log-rank test. Among 128 new ALL patients, 23 (18.0% patients suffered from CNS leukemia, while 13 (10.2% suffered from early CNS leukemia and 10 (7.8% suffered from relapsing CNS leukemia. CNS leukemia was more common in male, in those aged less than 2 years, in those with white blood cell (WBC count above 50,000/ìl, and in patients type FAB-L2 ALL. The clinical manifestations most commonly found were decrease of consciousness (61%, vomiting (48%, cranial nerve palsy (44%, seizures (39%, and headache (26%. Relapsing CNS leukemia was more common in high risk (12.5% compared with standard risk leukemia (5.7%. Patients with early CNS leukemia had a lower survival rate than those without early CNS leukemia (p = 0.0005. The percentage of patients with early CNS leukemia surviving up to 3 years was 26%. We conclude that early CNS leukemia could cause low survival ALL patients.

  18. Frequencies and prognostic impact of RAS mutations in MLL-rearranged acute lymphoblastic leukemia in infants

    NARCIS (Netherlands)

    E.M.C. Driessen; E.H.J. van Roon (Eddy); J.A.P. Spijkers-Hagelstein (J A P); P. Schneider (Pauline); P. de Lorenzo (Paola); M.G. Valsecchi (Maria Grazia); R. Pieters (Rob); R.W. Stam (Ronald)

    2013-01-01

    textabstractAcute lymphoblastic leukemia in infants represents an aggressive malignancy associated with a high incidence (approx. 80%) of translocations involving the Mixed Lineage Leukemia (MLL) gene. Attempts to mimic Mixed Lineage Leukemia fusion driven leukemogenesis in mice raised the question

  19. Childhood Acute Lymphoblastic Leukemia: Integrating Genomics into Therapy

    Science.gov (United States)

    Tasian, Sarah K; Loh, Mignon L; Hunger, Stephen P

    2015-01-01

    Acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, is a genetically complex entity that remains a major cause of childhood cancer-related mortality. Major advances in genomic and epigenomic profiling during the past decade have appreciably enhanced knowledge of the biology of de novo and relapsed ALL and have facilitated more precise risk stratification of patients. These achievements have also provided critical insights regarding potentially targetable lesions for development of new therapeutic approaches in the era of precision medicine. This review delineates the current genetic landscape of childhood ALL with emphasis upon patient outcomes with contemporary treatment regimens, as well as therapeutic implications of newly identified genomic alterations in specific subsets of ALL. PMID:26194091

  20. [Acute lymphoblastic leukemia of T progenitors: from biology to clinics].

    Science.gov (United States)

    Genescà, Eulàlia; Ribera, Jordi; Ribera, Josep-Maria

    2015-03-09

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children and the main cause of morbidity among childhood blood disorders. There are 2 subtypes according to the affected lymphoid progenitor: B-ALL and T-ALL. The T-ALL is the less common and, although historically was associated with poor prognosis in both adults and children, at present, treatment outcomes do not differ significantly between the 2 types of ALL. The T-ALL subtype is the most complex and heterogeneous at the genetic level and currently the one with less new therapeutic alternatives available. This trend is changing thanks to the remarkable progress upon understanding its biology. This review summarizes the most recent and important biological findings in T-ALL and their possible therapeutic implications. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  1. Treatment of Young Adults with Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Kansagra, Ankit; Litzow, Mark

    2017-06-01

    Young adults with acute lymphoblastic leukemia are a distinctive category of patients, with substantial difference in disease biology and response to therapy; hence, they pose unique challenges and issues beyond those faced by children and older adults. Despite inferior survival compared to children, there is growing evidence to suggest that young adults have improved outcomes when treated with pediatric-based approaches. With better supportive care and toxicity management and multidisciplinary team and approach, we have made great improvement in outcomes of young adults with ALL. However, despite significant progress, patients with persistence of minimal residual disease have a poor prognosis. This review discusses current controversies in the management of young adults with ALL, outcomes following pediatric and adult protocols, and the role of allogeneic stem cell transplantation. We also explore recent advances in disease monitoring and highlight our approach to incorporation of novel therapies in the management of young adults with ALL.

  2. 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.

  3. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

    Science.gov (United States)

    Schmiegelow, Kjeld; Müller, Klaus; Mogensen, Signe Sloth; Mogensen, Pernille Rudebeck; Wolthers, Benjamin Ole; Stoltze, Ulrik Kristoffer; Tuckuviene, Ruta; Frandsen, Thomas

    2017-01-01

    During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs. PMID:28413626

  4. 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...

  5. Acute Activation of Metabolic Syndrome Components in Pediatric Acute Lymphoblastic Leukemia Patients Treated with Dexamethasone

    NARCIS (Netherlands)

    Warris, Lidewij T.; van den Akker, Erica L. T.; Bierings, Marc B.; van den Bos, Cor; Zwaan, Christian M.; Sassen, Sebastiaan D. T.; Tissing, Wim J. E.; Veening, Margreet A.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2016-01-01

    Although dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), it can cause serious metabolic side effects. Because studies regarding the effects of dexamethasone are limited by their small scale, we prospectively studied the direct effects of treating

  6. Acute activation of metabolic syndrome components in pediatric acute lymphoblastic leukemia patients treated with dexamethasone

    NARCIS (Netherlands)

    Warris, Lidewij T.; Van Den Akker, Erica L T; Bierings, Marc B.; Van Bos, Cor Den; Zwaan, Christian M.; Sassen, Sebastiaan D T; Tissing, Wim J E; Veening, Margreet A.; Pieters, Rob; Van Den Heuvel-Eibrink, Marry M.

    2016-01-01

    Although dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), it can cause serious metabolic side effects. Because studies regarding the effects of dexamethasone are limited by their small scale, we prospectively studied the direct effects of treating

  7. Acute activation of metabolic syndrome components in pediatric acute lymphoblastic leukemia patients treated with dexamethasone

    NARCIS (Netherlands)

    L.T. Warris (Lidewij); E.L.T. van den Akker (Erica); M. Bierings (Marc); Van Bos, C.D. (Cor Den); C.M. Zwaan (Christian Michel); Sassen, S.D.T. (Sebastiaan D. T.); W.J.E. Tissing (Wim); M.A. Veening (Margreet A.); R. Pieters (Rob); M.M. van den Heuvel-Eibrink (Marry)

    2016-01-01

    textabstractAlthough dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), it can cause serious metabolic side effects. Because studies regarding the effects of dexamethasone are limited by their small scale, we prospectively studied the direct effects

  8. Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia

    Science.gov (United States)

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

    2011-06-01

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

  9. Effect of polymorphisms in folate-related genes on in vitro methotrexate sensitivity in pediatric acute lymphoblastic leukemia

    NARCIS (Netherlands)

    R. de Jonge (Robert); G.J. Peters (Godefridus); J.H. Hooijberg; B.D. van Zelst (Bertrand); G. Jansen (Gerrit); C.H. van Zantwijk; G.J. Kaspers (Gertjan); R. Pieters (Rob)

    2005-01-01

    textabstractWe studied whether common polymorphisms in genes involved in folate metabolism affect methotrexate (MTX) sensitivity. Ex vivo MTX sensitivity of lymphoblasts obtained from pediatric patients with acute lymphoblastic leukemia (ALL; n = 157) was determined by the in situ

  10. Immunological Subtypes of Acute Lymphoblastic Leukemia- Beyond Morphology: Experience from Kidwai State Cancer Institute, Bengaluru, India.

    Science.gov (United States)

    Rajkumar, Namrata N; Vijay, Raghavendra H

    2017-07-01

    Acute lymphoblastic leukemia (ALL) is disease of lymphoid precursors and is the most common cancer. Diagnosis of ALL is made by evaluating morphology and flowcytometric Immunophenotyping (FCI)and is an important adjunct in diagnosis and determining treatment in ALL, with availability of extensive monoclonal antibodies in the recent years there is tremendous progress in the field of FCI, and is a requirement by World Health Organisation for the classification of acute lymphoblastic Leukemia. Flow cytometric immunophenotyping of the leukemic blasts helps in categorization of acute lymphoblastic leukemia as B-ALL or T-ALL. Though ALL is the most common cancer, there is paucity of study in Indian scenario, and very few reports of immunologically subtyping of ALL is reported. To confirm the clinical/morphological diagnosis and to determine immunological subtype of acute lymphoblastic leukemia as per requirement by World Health Organization for the classification of acute lymphoblastic leukemia. At Kidwai State Cancer institute, Bangalore, we have performed of Immunophenotyping in 1425 untreated cases of acute leukemias during January 2012 - August 2015. Flow cytometry analysis of 1425 cases of acute Leukemias were performed, 918 (64.42%) were acute lymphoblastic Leukemia, 688 were B-ALL (74.94%), majority(480) of B-ALL were in children (69.76%), 230 were T-ALL (25.05 %), B-ALL was the most common subtype of acute leukemias. Acute lymphoblastic leukemia is the most common leukemia in adults and children. Immunophenotping helps in confirming the clinical/morphological diagnosis and in determining the immunological subtype of acute lymphoblastic leukemia, thus has an important role in deciding on the treatment regime. ALL is the disease of lymphoid precursors and is more common cancer in children than adults. B-ALL was the most common subtype of acute leukemias both in adults and in children. T-ALL is less common in pediatric population. Flowcytometric techniques are used

  11. 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.

  12. Paraneoplastic myopathy as a very rare manifestation of acute lymphoblastic leukemia.

    Science.gov (United States)

    Kameda, G; Vieker, S; Duck, C; Blaes, F; Längler, A

    2010-11-01

    We present a 9-year-old girl who developed acute muscular weakness of proximal muscles of the upper and lower limbs. Investigations revealed a common acute lymphoblastic leukemia. The neuromuscular symptoms are classified as a paraneoplastic neurological syndrome (PNS). Under chemotherapy according to ALL-BFM-2000 protocol symptoms resolved within 4 weeks. This case presents a rare manifestation of acute lymphoblastic manifestation. © Georg Thieme Verlag KG Stuttgart · New York.

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

    Science.gov (United States)

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

    2014-05-28

    Osteoporosis in children is rare and usually secondary to an underlying disease process whose diagnosis may be difficult to detect. Etiological factors responsible for osteoporosis secondary to chronic illness include immobility, pubertal delay and other hormonal disturbances. Rarely, it can be a manifestation of acute lymphoblastic leukemia. Most of the reported bone fracture incidences associated with acute lymphoblastic leukemia occur during the course of the chemotherapy, not at the point of the first symptoms of leukemic disease, as happened with the case presented here. A 7-year-old Asian Balinese boy presented with back pain. His anteroposterior pelvic radiograph showed osteoporotic bone. A bone age study revealed growth failure of his metacarpals, phalanges and sesamoid. His total bone mass density was 97% age-match. However, a peripheral blood smear showed normochromic anemia with thrombocytopenia. Immunophenotyping of his peripheral blood revealed no dominant markers, but a bone marrow aspiration confirmed a diagnosis of acute lymphoblastic leukemia. Osteoporosis was the only manifestation of the child's underlying acute lymphoblastic leukemia. Leukemia was diagnosed when his bone marrow was found to contain more than 25% blasts. Because of leucopenia, the immunophenotype failed to reveal a dominant marker in this case, thus we were unable to classify the acute lymphoblastic leukemia.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-04-15

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

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

    Science.gov (United States)

    Cole, Peter D.; Kamen, Barton A.

    2006-01-01

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

  17. Recent advances in pediatric acute lymphoblastic and myeloid leukemia.

    Science.gov (United States)

    Ravindranath, Yaddanapudi

    2003-01-01

    Acute leukemia is the most common form of childhood cancer and is the primary cause of cancer-related mortality in children. In the United approximately 3250 cases are diagnosed annually in children and adolescents younger than 20 years, of whom 2400 have acute lymphoblastic leukemia (ALL). Treatment results in childhood ALL continue to improve, and the expected current cure rates approach 75 to 80% of all children with ALL, including T-ALL and mature B-cell ALL, the two variants that, not too long ago, had a considerably poorer prognosis compared with the common form of BpALL. The most significant new development in the past 2 years has been the development of further evidence for fetal origin of childhood leukemias, and additional evidence to support the notion that postnatal events modulating the events of immune-mediated elimination of these leukemic clones play a major role in the eventual development of clinical disease. Other epidemiologic developments include (1) increased appreciation of the role of drug-metabolizing enzymes, both in determining the predisposition to leukemia and response to therapy; and (2) both clinical observations and gene expression studies seeming to identify a new approach to the evaluation and treatment of children with MLL (11q23) rearrangements. A most remarkable new development in the induction therapy of childhood leukemia and lymphoma in the United States is the use of urate oxidase for prevention of tumor lysis syndrome and the associated uric acid nephropathy. Drug resistance, determined either on leukemic blast cells in vitro or by studies of MRD, is being looked at critically in an effort to improve the treatment results further. Consolidation with HDMTX has gained wider popularity with the realization that effective CNS prophylaxis can be achieved with intrathecal therapy plus HDMTX for consolidation. In contrast to ALL, the progress in the therapy of acute myeloid leukemia (AML) lags behind, with cure rates of

  18. New monoclonal antibodies for the treatment of acute lymphoblastic leukemia.

    Science.gov (United States)

    Farhadfar, Nosha; Litzow, Mark R

    2016-10-01

    Monoclonal antibodies represent a major advance in treatment of acute lymphoblastic leukemia (ALL). Targeted delivery of these agents based on leukemic cell-surface receptor recognition, improves efficacy and minimizes off-target toxicity. The antigens CD19, CD20, CD22 and CD52, are the most common antigens to which monoclonal antibodies in B-cell ALL have been directed. Rituximab, an anti-CD20 antibody, in combination with conventional chemotherapy has been shown to improve survival in newly diagnosed CD20 positive B-cell ALL. Blinatumomab, a bispecific T-cell engager, as monotherapy in relapsed and refractory B-cell ALL resulted in prolonged relapse free survival. Inotuzumab ozogamicin, an anti-CD22 antibody, alone and in combination with chemotherapy has been promising in relapsed and refractory B-cell ALL. The effectiveness and safety of several newer monoclonal antibodies including ofatumumab, obinutuzumab, epratuzumab, denintuzumab mafodotin and moxetumomab pasudotox as single agents or in combination with a chemotherapeutic back bone are currently under investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. The molecular genetic makeup of acute lymphoblastic leukemia.

    Science.gov (United States)

    Mullighan, Charles G

    2012-01-01

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

  20. Longitudinal nutritional assessment in acute lymphoblastic leukemia during treatment.

    Science.gov (United States)

    Higashiyama, Yukie; Kojima, Chiaki; Kubota, Masaru; Nagai, Ayako; Watanabe, Ken-Ichiro; Adachi, Souichi; Usami, Ikuya

    2014-08-01

    A nutritional assessment of pediatric patients with cancer is important to improve their outcome. The number of longitudinal nutritional studies during treatment, however, is limited. The purpose of this study was to investigate the longitudinal changes in anthropometric measures and serum albumin level during chemotherapy in patients with acute lymphoblastic leukemia (ALL). We retrospectively reviewed the charts of 23 patients (19 boys, four girls) with ALL from April 2007 to March 2010. The median age at diagnosis was 4.5 years. Bodyweight, height, and serum albumin levels were measured at the start and the end point of each chemotherapy phase. At diagnosis, two patients (8.7%) were underweight and five patients (21.7%) were overweight according to body mass index z-score, while five patients were underweight and three (13.0%) were overweight according to Waterlow score. The prevalence of malnourished patients did not change significantly throughout chemotherapy by either assessment. The absolute scores in either assessment were significantly reduced at the sanctuary treatment phase. Low serum albumin (nutritional status under a similar chemotherapeutic regimen as assessed by anthropometric measures and albumin level differed among patients, careful observation of the nutritional status and intervention may be necessary at different phases of chemotherapy. © 2014 Japan Pediatric Society.

  1. Premature adiposity rebound in children treated for acute lymphoblastic leukemia.

    Science.gov (United States)

    Reilly, J J; Kelly, A; Ness, P; Dorosty, A R; Wallace, W H; Gibson, B E; Emmett, P M

    2001-06-01

    The adiposity rebound (AR), when body mass index begins to increase after its nadir in childhood, is a critical period for the regulation of energy balance and adult obesity risk. The aim of the present study was to test whether children treated for acute lymphoblastic leukemia (ALL) experience premature AR. This might, in part, explain their tendency to develop obesity. Timing of AR was assessed by visual inspection of body mass index plots in 68 patients treated for ALL in first remission. This sample comprised all eligible patients treated in Scotland between 1991 and 1998, age 30 months or less at the time of diagnosis. Timing of AR in patients was compared against a cohort of 889 healthy British children studied during the 1990s using the same method. AR occurred significantly earlier in the patients treated for ALL (chi(2) test, P < 0.001). The AR had occurred in 43% (29 of 68) of the patients and 4% (40 of 889) of the comparison group by age 37 months. At 49 months AR had occurred in 81% (55 of 68) of the patients and 21% (190 of 889) of the comparison group. Treatment of ALL is associated with a significantly advanced AR. This might, in part, explain the extremely high prevalence of obesity in long-term survivors. Clinical management should focus on minimizing excess weight gain during therapy to reduce long-term obesity risk.

  2. Coagulation profile during induction chemotherapy in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Sehgal, Shivali; Sharma, Sunita; Chandra, Jagdish; Nangia, Anita

    2017-01-01

    Thromboembolism in children with acute lymphoblastic leukemia (ALL) is most commonly reported after the initiation of antileukemic therapy, indicating a possible interaction of disease and therapy. To study the effect of induction chemotherapy on coagulation parameters in pediatric ALL patients. Thirty-seven newly diagnosed patients of ALL up to 18 years of age were evaluated along with 30 age- and sex-matched controls. At the time of diagnosis (day 0), various coagulation parameters were tested. These were sequentially analyzed on day 14 (after the completion of L-asparaginase doses) and on day 28 of therapy (after the completion of induction). Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, protein C (PC) activity, and protein S (PS) activity were done by a clot-based method. Antithrombin (AT) assay was performed by chromogenic method. D-dimer (D-DI), tissue plasminogen activator (tPA), and plasminogen activator inhibitor type 1 (PAI-1) levels were assayed by ELISA method. The statistical analysis was done using Statistical Package for Social Sciences version 17.0. No major change in PT and APTT was observed during chemotherapy; however, fibrinogen levels declined significantly (P = 0.04), following L-asparaginase treatment. D-DI levels were significantly raised at diagnosis (P chemotherapy cause thrombin activation, decrease in natural inhibitors, and hypofibrinolysis, resulting in hypercoagulability. Thus, ALL per se is a hypercoagulable state and the prothrombotic condition at the time of diagnosis gets enhanced during induction chemotherapy.

  3. Prevention of oral lesions in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Pereira Pinto, Leão; de Souza, Lélia Batista; Gordón-Núñez, Manuel Antonio; Soares, Rosilene Calasanz; de Brito Costa, Edja Maria Melo; de Aquino, Ana Rafaela Luz; Fernandes, Maria Zélia

    2006-11-01

    Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children and is responsible for severe stomatologic complications. Treatment consists of four phases of chemotherapy, the main side effect of methotrexate, the drug most used during the intensification phase, is oral mucositis. To evaluate the clinical aspects of the oral mucosa of children with ALL and to determine the effect of 0.12% chlorhexidine gluconate on the prevention of stomatologic complications in these patients. Thirty-three children treated for ALL ranging in age from 2 to 15 years, without distinction of gender or race, were submitted to visual examination, digital palpation of the oral mucosa and cytologic examination of the buccal mucosa, and divided into two groups: group I consisted of 23 children using an oral solution of 0.12% chlorhexidine gluconate twice a day, and group II consisted of 10 children who did not receive this solution. All children received daily oral hygiene care guided by the dentist throughout treatment. Mucositis was observed in six children of group I and eight of group II, and was characterized by erythema, edema and ulcers. Uniform cytologic findings were obtained for the two groups, with a clear predominance of cells of the intermediate layer in all smears, in addition to a perinuclear halo in 18% of the smears. The present results suggest that systematic preventive treatment with 0.12% chlorhexidine gluconate and oral hygiene care reduce the occurrence of oral complications in children with ALL undergoing antineoplastic chemotherapy.

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

    Directory of Open Access Journals (Sweden)

    Josep-Maria Ribera

    2014-07-01

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

  5. 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.)

  6. The use of optical microscope equipped with multispectral detector to distinguish different types of acute lymphoblastic leukemia

    Science.gov (United States)

    Pronichev, A. N.; Polyakov, E. V.; Tupitsyn, N. N.; Frenkel, M. A.; Mozhenkova, A. V.

    2017-01-01

    The article describes the use of a computer optical microscopy with multispectral camera to characterize the texture of blasts bone marrow of patients with different variants of acute lymphoblastic leukemia: B- and T- types. Specific characteristics of the chromatin of the nuclei of blasts for different types of acute lymphoblastic leukemia were obtained.

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

    Science.gov (United States)

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

  8. 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...

  9. Unilateral Malignant Pleural Effusion as an Initial Manifestation of Acute Lymphoblastic Leukemia: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    Sonia Chabbra

    2015-01-01

    Full Text Available Unilateral malignant pleural effusion as an initial manifestation that leads to the diagnosis of an underlying acute lymphoblastic leukemia is a rare event. Early and accurate diagnosis of this case is important for prompt and adequate therapy. We present the case of an18-year-old male who presented to the emergency department with severe respiratory distress. Chest X-ray revealed a unilateral massive right-sided pleural effusion. Cytological examination of the pleural fluid led to the diagnosis of underlying acute lymphoblastic leukemia. Subsequent hemogram, bone marrow aspirate and flow cytometry analysis confirmed the diagnosis of T-lineage acute lymphoblastic leukemia. The patient underwent induction chemotherapy which led to significant clinical improvement due to resolution of the pleural effusion. The patient is on follow up at present. This case report exemplifies and highlights the importance of cytopathological analysis of body cavity fluids in the diagnosis of underlying unsuspected malignancies.

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

    Science.gov (United States)

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

    2016-06-01

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

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Elhamy Rifky Abdel Khalek

    2015-01-01

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

  13. Transient Hyperglycemia in Hispanic Children With Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Baillargeon, Jacques; Langevin, Anne-Marie; Mullins, Judith; Ferry, Robert J.; DeAngulo, Guillermo; Thomas, Paul J.; Estrada, Jaime; Pitney, Aaron; Pollock, Brad H.

    2011-01-01

    Background Transient hyperglycemia occurs commonly during the treatment for childhood acute lymphoblastic leukemia (ALL). The purpose of this study was to examine the incidence of and risk factors for transient hyperglycemia during induction chemotherapy in Hispanic pediatric patients diagnosed with B-Precursor ALL. Procedure The study cohort consisted of 155 Hispanic pediatric patients diagnosed with ALL and treated at one of two South Texas pediatric oncology centers between 1993 and 2002. Hyperglycemia was defined as ≥2 glucose determinations of ≥200 mg/dl during the first 28 days of induction chemotherapy. Results Overall, 11.0% of the study cohort developed transient hyperglycemia during induction chemotherapy. Age and body mass index (BMI) were both positively associated with the risk of hyperglycemia. Females exhibited a substantially higher risk of hyperglycemia than males, but this association did not reach statistical significance after adjusting for other covariates. Among patients who developed hyperglycemia, 100% of those who required insulin were in the 13–18-year age group and reported a family history of diabetes. Hyperglycemic patients classified as obese (BMI ≥ 95 centile) were more than twice as likely to have required insulin therapy compared to overweight patients (BMI 85–<95 centile) and three times as likely to have required insulin compared to normal weight (BMI <85 centile) patients. Conclusions The incidence of chemotherapy-induced transient hyperglycemia in the present study cohort is comparable to that reported in previous pediatric ALL patients. This finding is interesting in view of the elevated prevalence of obesity and the underlying dietary behaviors in this Hispanic study cohort. PMID:15700246

  14. 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.

  15. A Case of Acute Tuberculous Pleuropneumonia in a Patient with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Snezana Zivanovic

    2010-01-01

    Full Text Available Respiratory system infections are the most common complications in immunocompromised cancer patients. We here report a 14-year-old male who was admitted to the hospital because of acute pneumonia, who had been diagnosed with acute lymphoblastic leukemia (ALL when he was 12 years old. A diagnosis of acute tuberculous pleuropneumonia was made based on clinical and radiographical findings, and Mycobacterium tuberculosis was identified by Ziehl-Neelson acid-fast stain and culture on Löwenstein-Jensen medium. Twenty months before pneumonia onset, the patient had been treated with immunosupressive therapy (ALL IC-BFM 2002 protocol.

  16. Cytogenetic Profile and Gene Mutations of Childhood Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Nawaf Alkhayat

    2017-07-01

    Full Text Available Background: Childhood acute lymphoblastic leukemia (ALL is characterized by recurrent genetic aberrations. The identification of those abnormalities is clinically important because they are considered significant risk-stratifying markers. Aims: There are insufficient data of cytogenetic profiles in Saudi Arabian patients with childhood ALL leukemia. We have examined a cohort of 110 cases of ALL to determine the cytogenetic profiles and prevalence of FLT3 mutations and analysis of the more frequently observed abnormalities and its correlations to other biologic factors and patient outcomes and to compare our results with previously published results. Materials and methods: Patients —We reviewed all cases from 2007 to 2016 with an established diagnosis of childhood ALL. Of the 110 patients, 98 were B-lineage ALL and 12 T-cell ALL. All the patients were treated by UKALL 2003 protocol and risk stratified according previously published criteria. Cytogenetic analysis —Chromosome banding analysis and fluorescence in situ hybridization were used to detect genetic aberrations. Analysis of FLT3 mutations —Bone marrow or blood samples were screened for FLT3 mutations (internal tandem duplications, and point mutations, D835 using polymerase chain reaction methods. Result: Cytogenetic analysis showed chromosomal anomalies in 68 out of 102 cases with an overall incidence 66.7%. The most frequent chromosomal anomalies in ALL were hyperdiploidy, t(9;22, t(12;21, and MLL gene rearrangements. Our data are in accordance with those published previously and showed that FLT3 mutations are not common in patients with ALL (4.7% and have no prognostic relevance in pediatric patients with ALL. On the contrary, t(9;22, MLL gene rearrangements and hypodiploidy were signs of a bad prognosis in childhood ALL with high rate of relapse and shorter overall survival compared with the standard-risk group ( P  = .031.The event-free survival was also found to be worse ( P

  17. 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,

  18. Efficacy and Toxicity of Asparaginases During Prospective Drug Monitoring in Patients With Childhood Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    W.H. Tong (Wing)

    2014-01-01

    markdownabstract__Abstract__ Intensified and effective asparaginase therapy is very important in modern treatment of childhood acute lymphoblastic leukemia. The use of native E.coli asparaginase in induction leads to a high rate of hypersensitivity reactions to PEGasparaginase in the

  19. Outcome of congenital acute lymphoblastic leukemia treated on the Interfant-99 protocol

    NARCIS (Netherlands)

    M.H. van der Linden (Marieke); M.G. Valsecchi (Maria Grazia); P. de Lorenzo (Paola); A. Möricke; G. Janka (Gritta); T.M. Leblanc (Thierry); M. Felice (Maria); A. Biondi (Andrea); M. Campbell (Myriam); I. Hann (Ian); J.E. Rubnitz (Jeffrey); J. Stary (Jan); T. Szczepanski (Tomasz); A. Vora (Ajay); A. Ferster (Alina); L. Hovi (Liisa); L.B. Silverman (Lewis); R. Pieters (Rob)

    2009-01-01

    textabstractAcute lymphoblastic leukemia (ALL) diagnosed in the first month of life (congenital ALL) is very rare. Although congenital ALL is often assumed to be fatal, no studies have been published on outcome except for case reports. The present study reports the outcome of 30 patients with

  20. 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

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

    NARCIS (Netherlands)

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

    1996-01-01

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

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

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

    Science.gov (United States)

    Lurie, Michelle; Kaufman, Nadeen

    2001-01-01

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

  4. 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

    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...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  6. Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    For acute lymphoblastic leukemia (ALL), the 5-year survival rate has improved significantly since 1975. Get information about risk factors, signs, diagnosis, molecular features, survival, risk-based treatment assignment, and induction and postinduction therapy for children and adolescents with newly diagnosed and recurrent ALL.

  7. Study of Posterior Reversible Encephalopathy Syndrome in Children With Acute Lymphoblastic Leukemia After Induction Chemotherapy.

    Science.gov (United States)

    Tang, Ji-Hong; Tian, Jian-Mei; Sheng, Mao; Hu, Shao-Yan; Li, Yan; Zhang, Li-Ya; Gu, Qing; Wang, Qi

    2016-03-01

    Increasing occurrence of posterior reversible encephalopathy syndrome has been reported in children with acute lymphoblastic leukemia. However, the etiology of posterior reversible encephalopathy syndrome is not clear. To study the possible pathogenetic mechanisms and treatment of this complication, we reported 11 cases of pediatric acute lymphoblastic leukemia who developed posterior reversible encephalopathy syndrome after induction chemotherapy. After appropriate treatment, the clinical symptoms of posterior reversible encephalopathy syndrome in most cases disappeared even though induction chemotherapy continued. During the 1-year follow-up, no recurrence of posterior reversible encephalopathy syndrome was observed. Although the clinical and imaging features of posterior reversible encephalopathy syndrome may be diverse, posterior reversible encephalopathy syndrome should be recognized as a possible important complication of acute lymphoblastic leukemia when neurologic symptoms appear. In line with previous reports, our study also indicated that posterior reversible encephalopathy syndrome was reversible when diagnosed and treated at an early stage. Thus, the occurrence of posterior reversible encephalopathy syndrome should be considered and investigated to optimize the early induction scheme of acute lymphoblastic leukemia treatment. © The Author(s) 2015.

  8. Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia | Office of Cancer Genomics

    Science.gov (United States)

    NCI's TARGET Initiative reported the discovery of a novel genetic marker for children with acute lymphoblastic leukemia (ALL) in the January 7, 2009, advance online edition of The New England Journal of Medicine. The genetic alteration identified, IKZF1, should improve clinicians' ability to identify high-risk patients and better assign these patients to appropriate therapy.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  10. Extremely low-frequency magnetic fields and survival from childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Schüz, J; Grell, K; Kinsey, S

    2012-01-01

    A previous US study reported poorer survival in children with acute lymphoblastic leukemia (ALL) exposed to extremely low-frequency magnetic fields (ELF-MF) above 0.3 μT, but based on small numbers. Data from 3073 cases of childhood ALL were pooled from prospective studies conducted in Canada...

  11. Tyrosine kinase fusion genes in pediatric BCR-ABL1-like acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Boer, Judith M.; Steeghs, Elisabeth M. P.; Marchante, João R. M.; Boeree, Aurélie; Beaudoin, James J.; Beverloo, H. Berna; Kuiper, Roland P.; Escherich, Gabriele; van der Velden, Vincent H. J.; van der Schoot, C. Ellen; de Groot-Kruseman, Hester A.; Pieters, Rob; den Boer, Monique L.

    2017-01-01

    Approximately 15% of pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by gene expression similar to that of BCR-ABL1-positive disease and unfavorable prognosis. This BCR-ABL1-like subtype shows a high frequency of B-cell development gene aberrations and tyrosine

  12. 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....

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

    NARCIS (Netherlands)

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

    1996-01-01

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

  14. Free Air Intraperitoneally During Chemotherapy for Acute Lymphoblastic Leukemia : Consider Pneumatosis Cystoides Intestinalis

    NARCIS (Netherlands)

    Groninger, Ellis; Hulscher, Jan B. F.; Timmer, Bert; Tamminga, Rienk Y. J.; Broens, Paul M. A.

    Intraperitoneal free air in a child with acute lymphoblastic leukemia (ALL) treated with induction chemotherapy is an ominous sign suspective of gastrointestinal perforation. We report a case of pneumatosis cystoides intestinalis (PCI) with free intraperitoneal air without bowel perforation in a

  15. 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.

    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

  16. 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

  17. 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

  18. Breast lump as an initial manifestation in acute lymphoblastic leukemia: an unusual presentation. A case report.

    Science.gov (United States)

    Mandal, Shramana; Jain, Shyama; Khurana, Nita

    2007-02-01

    Breast lump as a presenting manifestation of acute lymphoblastic lymphoma (ALL) leukemia is extremely rare. We report a case of a young female who presented with a breast lump clinically suggestive of fibroadenoma. On fine needle aspiration cytology, it was diagnosed as lymphoid malignancy, later confirmed as ALL using hematological investigations.

  19. PTPN2 negatively regulates oncogenic JAK1 in T-cell acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M. Kleppe (Maria); J. Soulier (Jean); V. Asnafi (Vahid); N. Mentens (Nicole); T. Hornakova (Tekla); L. Knoops (Laurent); S. Constantinescu (Stefan); F. Sigaux (François); J.P.P. Meijerink (Jules); P. Vandenberghe (Peter); M. Tartaglia (Marco); R. Foa (Robin); E. Macintyre; T. Haferlach (Torsten); J. Cools (Jan)

    2011-01-01

    textabstractWe have recently reported inactivation of the tyrosine phosphatase PTPN2 (also known as TC-PTP) through deletion of the entire gene locus in ∼ 6% of T-cell acute lymphoblastic leukemia (T-ALL) cases. T-ALL is an aggressive disease of the thymocytes characterized by the stepwise

  20. Cytomegalovirus induced hemophagocytic lymphocytic histiocytosis in two pediatric patients with acute lymphoblastic leukemia.

    Science.gov (United States)

    Waddell, Benjamin; Belcher, Chris; Willey, Emily

    2017-01-01

    Hemophagocytic lymphohistiocytosis (HLH) is a rare inflammatory condition with tissue destruction due to abnormal immune activation. We present a series of 2 cases of cytomegalovirus-induced HLH in children during maintenance chemotherapy for acute lymphoblastic leukemia. These cases emphasize the importance of considering secondary HLH in this high-risk subset of pediatric patients.

  1. Cytomegalovirus induced hemophagocytic lymphocytic histiocytosis in two pediatric patients with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Benjamin Waddell

    2017-01-01

    Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a rare inflammatory condition with tissue destruction due to abnormal immune activation. We present a series of 2 cases of cytomegalovirus-induced HLH in children during maintenance chemotherapy for acute lymphoblastic leukemia. These cases emphasize the importance of considering secondary HLH in this high-risk subset of pediatric patients.

  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

  3. 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

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

    NARCIS (Netherlands)

    Gordijn, M.S.; van Litsenburg, R.R.L.; 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.

  5. 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.

  6. 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.

    2014-01-01

    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. PMID:24598854

  7. Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Castor, A; Nilsson, L; Astrand-Grundstrom, [No Value; Buitenhuis, M; Ramirez, C; Anderson, K; Strombeck, B; Garwicz, S; Bekassy, AN; Schmiegelow, K; Lausen, B; Hokland, P; Lehmann, S; Juliusson, G; Johansson, B; Jacobsen, SEW

    The cellular targets of primary mutations and malignant transformation remain elusive in most cancers. Here, we show that clinically and genetically different subtypes of acute lymphoblastic leukemia ( ALL) originate and transform at distinct stages of hematopoietic development. Primary ETV6-RUNX1 (

  8. In childhood acute lymphoblastic leukemia, blasts at different stages of immunophenotypic maturation have stem cell properties

    NARCIS (Netherlands)

    le Viseur, Christoph; Hotfilder, Marc; Bomken, Simon; Wilson, Kerrie; Roettgers, Silja; Schrauder, Andre; Rosemann, Annegret; Irving, Julie; Stam, Ronald W.; Shultz, Leonard D.; Harbott, Jochen; Juergens, Heribert; Schrappe, Martin; Pieters, Rob; Vormoor, Josef

    We examined the leukemic stem cell potential of blasts at different stages of maturation in childhood acute lymphoblastic leukemia (ALL). Human leukemic bone marrow was transplanted intrafemorally into NOD/scid mice. Cells sorted using the B precursor differentiation markers CD19, CD20, and CD34

  9. Bilateral cytomegalovirus retinitis in a child with acute lymphoblastic leukemia while on maintenance chemotherapy

    Directory of Open Access Journals (Sweden)

    Vaidehi S. Dedania

    2016-08-01

    Full Text Available We report a case of bilateral cytomegalovirus retinitis in a 12 year-old with neutropenic fever after maintenance chemotherapy for acute lymphoblastic leukemia. Ophthalmologic examination for photophobia prompted a diagnosis of cytomegalovirus retinitis. With early diagnosis and prompt treatment, this patient had a favorable visual outcome.

  10. Pten mediates Myc oncogene dependence in a conditional zebrafish model of T cell acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Gutierrez, A.; Grebliunaite, R.; Feng, H.; Kozakewich, E.; Zhu, S.; Guo, F.; Payne, E.; Mansour, M.; Dahlberg, S.E.; Neuberg, D.S.; den Hertog, J.; Prochownik, E.V.; Testa, J.R.; Harris, M.; Kanki, J.P.; Look, A.T.

    2011-01-01

    The MYC oncogenic transcription factor is overexpressed in most human cases of T cell acute lymphoblastic leukemia (T-ALL), often downstream of mutational NOTCH1 activation. Genetic alterations in the PTEN-PI3K-AKT pathway are also common in T-ALL. We generated a conditional zebrafish model of T-ALL

  11. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-05-01

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

  13. Ras/Raf/MEK/ERK pathway activation in childhood acute lymphoblastic leukemia and its therapeutic targeting

    Directory of Open Access Journals (Sweden)

    Thomas eKnight

    2014-06-01

    Full Text Available Deregulation of the Ras/Raf/MEK/ERK pathway is a common event in childhood acute lymphoblastic leukemia and is caused by point mutation, gene deletion and chromosomal translocation of a vast array of gene types, highlighting its importance in leukemia biology. Pathway activation can be therapeutically exploited and may guide new therapies needed for relapsed ALL and other high risk subgroups.

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

    DEFF Research Database (Denmark)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas

    2014-01-01

    BACKGROUND: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. PROCEDURE: To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744...... had higher leukocyte count compared with patients with CNS1 (P symptoms....... Symptoms or clinical findings were present among 27 of 54 patients with CNS3 versus only 7 of 39 patients with CNS2 and 15 of 75 patients with TLP+ (P 

  15. Meningeal chloroma (granulocytic sarcoma) in acute lymphoblastic leukemia mimicking a falx meningioma.

    Science.gov (United States)

    Ahn, Jung Yong; Kwon, Seong Oh; Shin, Moon Soo; Kang, Shin Heh; Kim, Young Rae

    2002-10-01

    Isolated chloromas (granulocytic sarcomas) are rare tumors. Chloromas are masses composed of immature granulocytic cells. Granulocytic sarcoma occurs primarily in patients with acute myelogenous leukemia and may also arise in patients with other myeloproliferative disorders, but rarely in patients with acute lymphoblastic leukemia (ALL). When dural-based, granulocytic sarcoma may be indistinguishable from meningioma radiologically. We now describe one patient affected by ALL with isolated granulocytic sarcoma mimicking a falx meningioma as initial CNS relapses. These unusual clinical manifestation and radiological finding in ALL should be considered as recurrence of leukemia. Early detection and antileukemic treatment of granulocytic sarcoma are necessarily important for favorable prognosis.

  16. "PATHOLOGIC FRACTURE OF THREE EXTREMITIES AS FIRST SIGN OF ACUTE LYMPHOBLASTIC LEUKEMIA "

    Directory of Open Access Journals (Sweden)

    S. Al-Yasin

    2007-05-01

    Full Text Available Acute lymphoblastic leukemia (ALL is the most common form of childhood cancer representing 80-85% of all leukemia. We describe a 3 years old girl with pain, swelling and tenderness in extremities since 8 months prior to her present admission. X-ray of extremities revealed callus formation, osteopenia and site of healed fractures. Bone marrow aspiration revealed ALL-L2 with normal peripheral smear. It is important for physician to recognize the skeletal manifestations of acute leukemia of childhood because a delay in diagnosis has an adverse effect on survival.

  17. Unilateral hypopyon in a child as a first and sole presentation in relapsing acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Wadhwa Neeraj

    2007-01-01

    Full Text Available Ocular manifestations form a part of the spectrum of varied clinical presentations in leukemias. Most of the ophthalmic manifestations are related to central nervous system leukemia and bone marrow relapse. We report a case of acute unilateral hypopyon uveitis as an initial presenting feature of relapsing acute lymphoblastic leukemia (ALL in a pediatric patient. Anterior chamber paracentesis was performed in a four-year-old male child presenting with unilateral treatment-resistant hypopyon after remission of ALL. Examination of aqueous humor aspirate revealed presence of malignant cells. Atypical hypopyon, even unilateral can be an indication of relapsing ALL in a child.

  18. 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.

  19. High-resolution genomic profiling of pediatric lymphoblastic lymphomas reveals subtle differences with pediatric acute lymphoblastic leukemias in the B-lineage.

    NARCIS (Netherlands)

    Schraders, M.; Reijmersdal, S.V. van; Kamping, E.J.; Krieken, J.H.J.M. van; Geurts van Kessel, A.H.M.; Groenen, P.J.T.A.; Hoogerbrugge, P.M.; Kuiper, R.P.

    2009-01-01

    Lymphoblastic lymphoma (LBL) is one of the most frequent occurring pediatric non-Hodgkin lymphomas. In the WHO classification scheme, pediatric LBL is considered to be the same disease entity as pediatric acute lymphoblastic leukemia (ALL). However, it is unclear whether the genetic basis of

  20. Novel cryptic chromosomal rearrangements detected in acute lymphoblastic leukemia detected by application of new multicolor fluorescent in situ hybridization approaches

    NARCIS (Netherlands)

    Karst, C; Gross, M; Haase, D; Wedding, U; Hoffken, K; Liehr, T; Mkrtchyan, H

    Routine cytogenetic analysis provides important information on diagnostic and prognostic relevance for hematological malignancies. However, it is often difficult to obtain good karyotypes, especially of cells from cases with acute lymphoblastic leukemia (ALL) because of poor morphology and

  1. 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

    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

  2. Gum hypertrophy - an unusual presenting feature in a case of precursor T-cell acute lymphoblastic leukemia

    National Research Council Canada - National Science Library

    Premalata, Chennagiri Srinivasamurthy; Madhumati, Davanam Satyanarayana; Lakshmidevi, Vishweshwariah; Pradeep, Rudramurthy; Appaji, Lingappa; Mukherjee, Geetashree

    2008-01-01

    ... and the central nervous system. We present a rare case of precursor T-cell acute lymphoblastic leukemia/lymphoma with initial oral manifestation, presenting with the unusual features of gum hypertrophy and involvement of upper jaw...

  3. Asparaginase-associated pancreatitis is not predicted by hypertriglyceridemia or pancreatic enzyme levels in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Raja, Raheel Altaf; Schmiegelow, Kjeld; Sørensen, Ditte Nørbo

    2017-01-01

    Background: l-Asparaginase is an important drug for treatment of childhood acute lymphoblastic leukemia (ALL), but is associated with serious toxicities, including pancreatitis and hypertriglyceridemia (HTG). Asparaginase-associated pancreatitis (AAP) is a common reason for stopping asparaginase...

  4. Epigenetic inactivation of TWIST2 in acute lymphoblastic leukemia modulates proliferation, cell survival and chemosensitivity

    Science.gov (United States)

    Thathia, Shabnam H.; Ferguson, Stuart; Gautrey, Hannah E.; van Otterdijk, Sanne D.; Hili, Michela; Rand, Vikki; Moorman, Anthony V.; Meyer, Stefan; Brown, Robert; Strathdee, Gordon

    2012-01-01

    Background Altered regulation of many transcription factors has been shown to be important in the development of leukemia. TWIST2 modulates the activity of a number of important transcription factors and is known to be a regulator of hematopoietic differentiation. Here, we investigated the significance of epigenetic regulation of TWIST2 in the control of cell growth and survival and in response to cytotoxic agents in acute lymphoblastic leukemia. Design and Methods TWIST2 promoter methylation status was assessed quantitatively, by combined bisulfite and restriction analysis (COBRA) and pyrosequencing assays, in multiple types of leukemia and TWIST2 expression was determined by quantitative reverse transcriptase polymerase chain reaction analysis. The functional role of TWIST2 in cell proliferation, survival and response to chemotherapy was assessed in transient and stable expression systems. Results We found that TWIST2 was inactivated in more than 50% of cases of childhood and adult acute lymphoblastic leukemia through promoter hypermethylation and that this epigenetic regulation was especially prevalent in RUNX1-ETV6-driven cases. Re-expression of TWIST2 in cell lines resulted in a dramatic reduction in cell growth and induction of apoptosis in the Reh cell line. Furthermore, re-expression of TWIST2 resulted in increased sensitivity to the chemotherapeutic agents etoposide, daunorubicin and dexamethasone and TWIST2 hypermethylation was almost invariably found in relapsed adult acute lymphoblastic leukemia (91% of samples hypermethylated). Conclusions This study suggests a dual role for epigenetic inactivation of TWIST2 in acute lymphoblastic leukemia, initially through altering cell growth and survival properties and subsequently by increasing resistance to chemotherapy. PMID:22058208

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

    Directory of Open Access Journals (Sweden)

    Marc Heincelman MD

    2016-09-01

    Full Text Available 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.

  6. Frequency of chromosomally-integrated human herpesvirus 6 in children with acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Annie Gravel

    Full Text Available Human herpesvirus 6 (HHV-6 is a ubiquitous pathogen infecting nearly 100% of the human population. Of these individuals, between 0.2% and 1% of them carry chromosomally-integrated HHV-6 (ciHHV-6. The biological consequences of chromosomal integration by HHV-6 remain unknown.To determine and compare the frequency of ciHHV-6 in children with acute lymphoblastic leukemia to healthy blood donors.A total of 293 DNA samples from children with pre-B (n=255, pre-pre-B (n=4, pre-T (n=26 and undetermined (n=8 leukemia were analyzed for ciHHV-6 by quantitative TaqMan PCR (QPCR using HHV-6 specific primers and probe. As control, DNA samples from 288 healthy individuals were used. Primers and probe specific to the cellular GAPDH gene were used to estimate integrity and DNA content.Out of 293 DNA samples from the leukemic cohort, 287 contained amplifiable DNA. Of these, only 1 (0.35% contained ciHHV-6. Variant typing indicates that the ci-HHV-6 corresponds to variant A. None of the 288 DNA samples from healthy individuals contained ciHHV-6.The frequency of ciHHV-6 in children with acute lymphoblastic leukemia is similar (p=0.5 to that of healthy individuals. These results suggest that acute lymphoblastic leukemia does not originate as a consequence to integration of HHV-6 within the chromosomes.

  7. Computerized psychometry screening in long-term survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    O'Hare, A E; Aitken, K; Eden, O B

    1988-01-01

    This study assessed the diagnostic utility of a computerized psychometry battery of tests: the Bexley-Maudsley Automated Psychological Screening Test and Category Sorting Test in the screening for deficits in cognitive function in a population of children who had been treated for acute lymphoblastic leukemia. Central nervous system therapy with radiotherapy and intrathecal chemotherapy has been incriminated as a cause of psychological morbidity in survivors. Twenty-nine children who were surviving in their first hematological remission, following cessation of their treatment for acute lymphoblastic leukemia, were studied. No child had evidence of central nervous system leukemic involvement, and they were all attending normal schools. Their performances were compared with 29 control children matched by age, sex, and social class. The children treated for leukemia showed a reduced ability to sustain attention (p less than 0.025), a reduction in verbal recognition short term memory (p less than 0.02), and difficulties in abstract problem solving (p less than 0.01). These results confirm the presence of neurophysical morbidity in children treated for acute lymphoblastic leukemia. It is suggested that this computerized psychometry test battery is a useful method for examining children at risk of neurological impairment and identifies specific deficits that require further evaluation and remedial help.

  8. Oral manifestations leading to the diagnosis of acute lymphoblastic leukemia in a young girl.

    Science.gov (United States)

    Silva, B A; Siqueira, C R B; Castro, P H S; Araújo, S S; Volpato, L E R

    2012-01-01

    oral complications may be leukemia's first presentation. to present a case of a young girl with a swelling on the face that led to the diagnosis of acute lymphoblastic leukemia is reported. a 10-year old anemic girl was referred for evaluation and treatment of a swelling at the left-nasolabial region. Symptoms reported (tiredness, poor appetite, fever, lethargy, and musculoskeletal pain) and clinical findings (enlargement at the presternal region and brownish stain in the lumbar region) led to the suspicion of a hematopoietic malignancy. The diagnosis of lymphoblastic leukemia was attained after specific examination conducted by the pediatric oncologist and hematologist. dentists must be able to clearly recognize oral physiological characteristics, and, when identifying changes of normalcy, to fully investigate it requesting additional tests or referring the patient to specialized professionals.

  9. [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.

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

    Directory of Open Access Journals (Sweden)

    Zhao J

    2015-06-01

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

  11. Breast tumour as the first manifestation of extramedullary relapse of Philadelphia positive (Ph+) acute lymphoblastic leukemia.

    Science.gov (United States)

    Dragoumis, Dimitrios M; Kyropoulou, Aikaterini N; Desiris, Klearchos I; Assimaki, Anthoula S; Tsiftsoglou, Aris P

    Extramedullary relapses of acute lymphoblastic leukemia (ALL) are rare and usually localized in the central nervous system. We describe such an uncommon case of extramedullary relapse of ALL in the breast of a 44 year old female. The patient, who had been diagnosed with precursor B cell, Philadelphia positive (Ph+) acute lymphoblastic leukemia (ALL) 5 years before and had been in complete molecular remission for the last 19 months, was admitted to the hospital for investigation of a hard, non-tender lump in her right breast. Mammography detected a dense, ill-defined mass, whereas on grey-scale and power Doppler sonography, the appearance of the lesion was consistent with malignancy. Histopathologic and immunohistochemical examination of the specimen demonstrated a similar immunophenotype (CD20+, CD10+, Tdt+, CD3-) as this of the onset ALL cell population in the bone marrow.

  12. [Ocular manifestations of acute T-cell lymphoblastic leukemia in hematological remission--a case report].

    Science.gov (United States)

    Siedlińska, Maria; Karska-Basta, Izabella; Pagacz, Dominika; Sobociński, Marcin; Romanowska-Dixon, Bożena

    2014-01-01

    The paper presents a case of a 60 year-old female referred to the Department of Ophthalmology and Ocular Oncology, Medical College, Jagiellonian University in Krakow with the sudden severe vision deterioration in both eyes. The patient was treated for T-cell acute lymphoblastic leukemia at the local Department of Hematology, at that time she was considered to be in hematological remission. Based on findings of clinical examination and additional tests, the patient was diagnosed with leukemic infiltration of the retina and optic nerve with secondary retinal detachment. Systemic and intrathecal chemotherapy as well as local radiotherapy to both eyes were administered. Ocular manifestations of T-cell acute lymphoblastic leukemia may develop in patients in hematological remission. Standard management of leukemic infiltrates involving the retina, choroid and optic nerve includes the intrathecal chemotherapy and lo- cal radiotherapy. Such therapy caused regression and cicatrization of the ocular infiltrates, but did not improve visual acuity in the described patient.

  13. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Kjeld Schmiegelow

    2017-04-01

    Full Text Available During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both, bone toxicities (including osteonecrosis, thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia, high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs.

  14. Radiation-free allogeneic conditioning with fludarabine, carmustine, and thiotepa for acute lymphoblastic leukemia and other hematologic malignancies necessitating enhanced central nervous system activity

    National Research Council Canada - National Science Library

    Christopoulos, Petros; Bertz, Hartmut; Ihorst, Gabriele; Marks, Reinhard; Wäsch, Ralph; Finke, Jürgen

    2012-01-01

    .... For less-fit patients with acute lymphoblastic leukemia and other hematologic malignancies frequently affecting the central nervous system, we designed a radiation-free regimen with fludarabine...

  15. 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

  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. Relationship between the general condition of acute lymphoblastic leukemia patients with remission rate and convulsion as an adverse effect chemotherapy

    Directory of Open Access Journals (Sweden)

    Rusdi Andid

    2017-02-01

    Full Text Available A retrospective study on the relationship between the general condition of acute lymphoblastic leukemia patients with remission rale and convulsion as an adverse effect of chemotherapy was conducted in leukemia patients of the hematology-oncology subdivision, Departmenl of Child Health, Medical School, University of North Sumatra, Medan. Of 114 children with acute lymphoblastic leukemia, 81 (71.05% received chemotherapy, 31 patients among them was in good general condition. Remission rate of the 31 patients was 80.6% (25 children. Whereas in the remaining 50 patients, the remission rate among them was 84% (42 patients. There was no significant relationship between their general condition to the recurrence rate of acute lymphoblastic leukemia patients who had been administered chemotherapy during induction phase. Convulsion was found In 2 cases, due to CNS leukemia.

  18. CD22: A Promising Target for Acute Lymphoblastic Leukemia Treatment | Center for Cancer Research

    Science.gov (United States)

    There are about 4,000 new cases of acute lymphoblastic leukemia (ALL) in the United States each year. Great improvements have been made in the treatment of ALL, but many patients suffer from side effects of standard therapy and continue to die of this disease. One of the most promising therapeutic strategies includes engineering T cells with a chimeric antigen receptor (CAR) that alters T cell specificity and function to recognize tumor antigens.

  19. 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.

  20. 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...... of cardiomyopathy were present in patients treated in childhood with cumulative anthracycline doses of less than 300 mg/m(2)....

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

    OpenAIRE

    Hale Ören; Şebnem Yılmaz; Özlem Tüfekçi; Mustafa Kır; Ece Böber; Gülersu İrken; Pakize Karakaya

    2013-01-01

    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. Endocrinologic...

  2. Initial Presentation of Acute Lymphoblastic Leukemia with Osteoporosis and Multiple Spontaneous Bone Fractures

    OpenAIRE

    Cohan, N; Sarikhani, S; Moslemi, S; Karimi, M.

    2011-01-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Skeletal abnormalities have been described in association with ALL including osteoprosis and bone fractures. Different factors including the disease itself or soluble products of malignant cells and treatment agents like cytotoxic drugs, methotroxate, corticosteroids and radiotherapy may be responsible for defective bone homeostasis in these patients. Orthopedic conditions and pain may be the first manifestation of ac...

  3. Early presentation of osteonecrosis in acute lymphoblastic leukemia: Two children from the Nordic and Baltic cohort.

    Science.gov (United States)

    Mogensen, Signe Sloth; Harila-Saari, Arja; Frandsen, Thomas Leth; Lähteenmäki, Päivi; Castor, Anders; Kohonen, Ia; Schmiegelow, Kjeld; Mäkitie, Outi

    2017-11-01

    Osteonecrosis (ON) is usually considered treatment related in patients with acute lymphoblastic leukemia (ALL). We report two patients with presentation of ON at the time of ALL diagnosis. Both were females and diagnosed with ALL at age 8 and 14 years. In the latter, some symptoms and radiologically verified ON in both knees were still present after the end of ALL therapy. No pediatric patients have previously been reported with ON presenting before initiation of ALL therapy. © 2017 Wiley Periodicals, Inc.

  4. Atherogenic low density lipoprotein phenotype in long-term survivors of childhood acute lymphoblastic leukemia

    OpenAIRE

    Malhotra, Jyoti; Tonorezos, Emily S.; Rozenberg, Marina; Vega, Gloria L.; Sklar, Charles A.; Chou, Joanne; Moskowitz, Chaya S.; Eshelman-Kent, Debra A.; Janiszewski, Peter; Ross, Robert; Oeffinger, Kevin C.

    2012-01-01

    Survivors of childhood acute lymphoblastic leukemia (ALL) have an increased risk of cardiovascular disease. Small density lipoproteins are atherogenic but have not been studied in this population. We conducted a cross-sectional analysis of 110 ALL survivors (mean age, 24.3 years) to determine prevalence of small dense LDL (pattern B) phenotype in ALL survivors and identify associated factors. Lipid subfractions were measured using Vertical Auto Profile-II. Participants with greater than 50% o...

  5. 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.

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

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    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.

  7. 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.

  8. Altered brain function in new onset childhood acute lymphoblastic leukemia before chemotherapy: A resting-state fMRI study.

    Science.gov (United States)

    Hu, Zhanqi; Zou, Dongfang; Mai, Huirong; Yuan, Xiuli; Wang, Lihong; Li, Yue; Liao, Jianxiang; Liu, Liwei; Liu, Guosheng; Zeng, Hongwu; Wen, Feiqiu

    2017-10-01

    Cognitive impairments had been reported in childhood acute lymphoblastic leukemia, what caused the impairments needed to be demonstrated, chemotherapy-related or the disease itself. The primary aim of this exploratory investigation was to determine if there were changes in brain function of children with acute lymphoblastic leukemia before chemotherapy. In this study, we advanced a measure named regional homogeneity to evaluate the resting-state brain activities, intelligence quotient test was performed at same time. Using regional homogeneity, we first investigated the resting state brain function in patients with new onset childhood acute lymphoblastic leukemia before chemotherapy, healthy children as control. The decreased ReHo values were mainly founded in the default mode network and left frontal lobe, bilateral inferior parietal lobule, bilateral temporal lobe, bilateral occipital lobe, precentral gyrus, bilateral cerebellum in the newly diagnosed acute lymphoblastic leukemia patients compared with the healthy control. While in contrast, increased ReHo values were mainly shown in the right frontal lobe (language area), superior frontal gyrus-R, middle frontal gyrus-R and inferior parietal lobule-R for acute lymphoblastic leukemia patients group. There were no significant differences for intelligence quotient measurements between the acute lymphoblastic leukemia patient group and the healthy control in performance intelligence quotient, verbal intelligence quotient, total intelligence quotient. The altered brain functions are associated with cognitive change and language, it is suggested that there may be cognition impairment before the chemotherapy. Regional homogeneity by functional magnetic resonance image is a sensitive way for early detection on brain damage in childhood acute lymphoblastic leukemia. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  9. Causes of death - other than progressive leukemia - in childhood acute lymphoblastic (ALL) and myeloid leukemia (AML) : the Dutch Childhood Oncology Group experience

    NARCIS (Netherlands)

    Slats, AM; Egeler, RM; van der Does-van den Berg, A; Korbijn, C; Hahlen, K; Kamps, WA; Veerman, AJP; Zwaan, CM

    We analyzed causes of death, other than resistant disease or relapse, in 875 children with acute lymphoblastic leukemia ( ALL) and 229 with acute myeloid leukemia (AML), treated on three different Dutch Childhood Oncology Group (DCOG) ALL and three AML protocols. Overall, 23 (2.6%) ALL and 44

  10. Oral manifestations leading to the diagnosis of acute lymphoblastic leukemia in a young girl

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    B A Silva

    2012-01-01

    Full Text Available Background: oral complications may be leukemia′s first presentation. Aim: to present a case of a young girl with a swelling on the face that led to the diagnosis of acute lymphoblastic leukemia is reported. Results: a 10-year old anemic girl was referred for evaluation and treatment of a swelling at the left-nasolabial region. Symptoms reported (tiredness, poor appetite, fever, lethargy, and musculoskeletal pain and clinical findings (enlargement at the presternal region and brownish stain in the lumbar region led to the suspicion of a hematopoietic malignancy. The diagnosis of lymphoblastic leukemia was attained after specific examination conducted by the pediatric oncologist and hematologist. Conclusion: dentists must be able to clearly recognize oral physiological characteristics, and, when identifying changes of normalcy, to fully investigate it requesting additional tests or referring the patient to specialized professionals.

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

    DEFF Research Database (Denmark)

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

    1983-01-01

    Fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA) were purified from both fetal liver and fetal bone marrow by immune rosetting with sheep erythrocytes coated with rabbit anti-mouse immunoglobulin and by fluorescence-activated cell sorting. Dual...... lymphoblastic leukemia cell with respect to surface marker phenotype. A population of CALLA- cells devoid of mature erythroid and myeloid surface markers was found to contain higher numbers of TdT+ cells but lower numbers of cyto-mu, B1, and Ia+ cells than the CALLA+ subset. In vitro analysis of normal...... 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...

  12. Bilateral parotidomegaly as an initial manifestation of acute lymphoblastic leukemia in a child: A case report and review of literature

    OpenAIRE

    Sneha, Latha Magatha; Subbiah, Kaarthikeyani Sankaravadivelu; Scott, Julius Xavier; Rajendiran, Aruna

    2017-01-01

    The more common causes of parotid enlargement in children are infections and inflammatory conditions. Primary neoplasms of the parotid glands are rare in pediatric age group; however, secondary malignancies have been reported in survivors of childhood leukemia. The parotid glands have been the sites of relapses in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia. However, bilateral parotid involvement as an initial presentation of ALL is rarely reported. We present a case of an 8...

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

    Science.gov (United States)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas; Forestier, Erik; Frandsen, Thomas L; Harila-Saari, Arja; Heyman, Mats; Jonsson, Olafur G; Lähteenmäki, Päivi M; Lausen, Birgitte; Vaitkevičienė, Goda; Asberg, Ann; Schmiegelow, Kjeld

    2014-08-01

    Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744 patients on Nordic-Baltic trials. CNS status was classified as CNS1 (no CSF blasts), CNS2 ( 0.15). The 12-year event-free survival for patients with leukemic mass on neuroimaging did not differ from patients with negative or no scan (0.50 vs. 0.60; P = 0.7) or between patients with symptoms or signs suggestive of CNS leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia. © 2014 Wiley Periodicals, Inc.

  14. Favorable outcome after 1-year treatment of childhood T-cell lymphoma/T-cell acute lymphoblastic leukemia

    NARCIS (Netherlands)

    van den Berg, H.; Zsiros, J.; Veneberg, A.; Schutten, N. J.; Kroes, W.; Slater, R. M.; Behrendt, H.

    1998-01-01

    For T-malignancies in children a poor prognosis is reported. In these malignancies a combination of lymphoma and leukemia is commonly seen at presentation and most patients are treated according to protocols for acute lymphoblastic leukemia (ALL). These protocols are often designed for the majority

  15. Discrimination of acute lymphoblastic leukemia from systemic-onset juvenile idiopathic arthritis at disease onset

    Science.gov (United States)

    Tamashiro, Mirian S; Aikawa, Nádia Emi; Campos, Lucia Maria A; Cristofani, Lílian Maria; Odone-Filho, Vicente; Silva, Clovis A

    2011-01-01

    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

  16. Discrimination of acute lymphoblastic leukemia from systemic-onset juvenile idiopathic arthritis at disease onset

    Directory of Open Access Journals (Sweden)

    Mirian S. Tamashiro

    2011-01-01

    Full Text Available OBJECTIVE: To assess clinical and laboratory features that differentiate acute lymphoblastic leukemia from systemic juvenile idiopathic arthritis at disease onset. METHODS: Fifty-seven leukemia patients with musculoskeletal involvement, without blasts on peripheral blood and without glucocorticoid therapy at disease onset and 102 systemic juvenile idiopathic arthritis patients (International League of Associations for Rheumatology criteria were retrospectively evaluated. The following features were examined: fever, rheumatoid rash, arthritis, limb pain, hepatomegaly, splenomegaly, pericarditis, myocarditis, pleuritis, weight loss, bleeding, anemia, leukopenia, neutropenia, thrombocytopenia, erythrocyte sedimentation rate, and lactic dehydrogenase levels. RESULTS: The median age at disease onset was significantly higher in leukemia patients than in those with systemic-onset juvenile idiopathic arthritis (5.8 vs. 3.8 years. In addition, the frequencies of limb pain, hepatomegaly, weight loss and hemorrhagic manifestations were significantly higher in leukemia patients than in systemic-onset juvenile idiopathic arthritis patients (70% vs. 1%, 54% vs. 32%, 30% vs. 8%, and 9% vs. 0%, respectively. Likewise, the frequencies of anemia, leukopenia, neutropenia, thrombocytopenia and high lactic dehydrogenase levels were statistically higher in leukemia patients than in patients with systemic-onset juvenile idiopathic arthritis (88% vs. 57%, 39% vs. 1%, 60% vs. 1%, 77% vs. 1%, and 56% vs. 14%, respectively. Remarkably, multivariate analysis revealed that limb pain (OR = 553; 95% CI =46.48-6580.42 and thrombocytopenia (OR = 754.13; 95% CI =64.57-8806.72 were significant independent variables that differentiated leukemia from systemic-onset juvenile idiopathic arthritis. The R2 of the Nagelkerke test was 0.91, and the Kaplan-Meier survival curves were similar for acute lymphoblastic leukemia patients with and without limb pain. CONCLUSION: Our study

  17. An unusual presentation of pediatric acute lymphoblastic leukemia with parotid gland involvement and dactylitis

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    Şule Ünal

    2010-06-01

    Full Text Available Mumps infection during the course of childhood acute lymphoblastic leukemia (ALL treatment has been reported to have a mild course and this was related to the intrinsic low cytopathological effect of the virus, contrasting with the severe course of measles and Varicella zoster virus infections in immunocompromised patients. Herein, we present a three-year-old girl, who was previously vaccinated against mumps infection, admitted with bilateral parotid swelling, dactylitis and serum immunoglobulin M positivity for mumps infection and diagnosed to have ALL with bilateral persistent parotid involvement, inconsistent with mumps infection. Acute leukemia should be suspected during the atypical course of any disease during childhood. Besides, mumps infection at presentation of ALL, as similar to infection emerging during the period of the leukemia treatment, has a mild course.

  18. Methotrexate-induced chemical meningitis in patients with acute lymphoblastic leukemia/lymphoma

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    Linu A Jacob

    2015-01-01

    Full Text Available Background: Intrathecal methotrexate (ITMTX is an important component in the treatment as well as prophylaxis of leukemia/lymphoma. ITMTX can cause chemical meningitis characterized by vomiting, headache, and fever lasting 2-5 days with spontaneous resolution of symptoms which differentiates this syndrome from bacterial meningitis. Objective: This prospective observational study was carried out to determine incidence of post-ITMTX syndrome in patients receiving prophylactic ITMTX as part of Berlin-Frankfurt-Munster (BFM protocol. Materials and Methods: Patients aged 15-50 years receiving BFM 90 or BFM 95 protocol for acute lymphoblastic leukemia or lymphoblastic lymphoma were followed up for post-ITMTX syndrome, defined as vomiting, headache and fever between 38 o and 39 o C following ITMTX. Results: Thirty-three patients received a total of 297 courses of ITMTX. Of the 297 doses of ITMTX, 20 episodes (6.7% of post-ITMTX syndrome were observed. The incidence of post-ITMTX syndrome was highest after the second dose of ITMTX (24%. The most common symptom of post-ITMTX syndrome was headache which was seen in 17 (85% patients. Seventeen (85% patients had vomiting, 10 (50% patients had fever, and 4 (20% patients had backache. Meningeal signs were present in 2 (10% patients. Conclusions: Post-ITMTX syndrome is not uncommon in adult patients receiving prophylactic ITMTX for treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Patients develop a toxic syndrome closely mimicking acute bacterial meningitis but spontaneous recovery is seen without any neurological sequelae.

  19. Flavopiridol and Vorinostat in Treating Patients With Relapsed or Refractory Acute Leukemia or Chronic Myelogenous Leukemia or Refractory Anemia

    Science.gov (United States)

    2013-04-01

    Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Relapsing Chronic Myelogenous Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  20. 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.

  1. 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

  2. Intragenic ERG Deletions Do Not Explain the Biology of ERG-Related Acute Lymphoblastic Leukemia.

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    Eliska Potuckova

    Full Text Available Intragenic ERG deletions occur in 3-5% of B-cell precursor acute lymphoblastic leukemia, specifically in B-other subtype lacking the classifying genetic lesions. They represent the only genetic lesion described so far present in the majority of cases clustering into a subgroup of B-other subtype characterized by a unique gene expression profile, probably sharing a common, however, not yet fully described, biological background. We aimed to elucidate whether ERG deletions could drive the specific biology of this ERG-related leukemia subgroup through expression of aberrant or decreased expression of wild type ERG isoforms. We showed that leukemic cells with endogenous ERG deletion express an aberrant transcript translated into two proteins in transfected cell lines and that one of these proteins colocalizes with wild type ERG. However, we did not confirm expression of the proteins in acute lymphoblastic leukemia cases with endogenous ERG deletion. ERG deletions resulted in significantly lower expression of wild type ERG transcripts compared to B-other cases without ERG deletion. However, cases with subclonal ERG deletion, clustering to the same ERG deletion associated subgroup, presented similar levels of wild type ERG as cases without ERG deletion. In conclusion, our data suggest that neither the expression of aberrant proteins from internally deleted allele nor the reduced expression of wild type ERG seem to provide a plausible explanation of the specific biology of ERG -related leukemia subgroup.

  3. CREBBP knockdown enhances RAS/RAF/MEK/ERK signaling in Ras pathway mutated acute lymphoblastic leukemia but does not modulate chemotherapeutic response.

    Science.gov (United States)

    Dixon, Zach A; Nicholson, Lindsay; Zeppetzauer, Martin; Matheson, Elizabeth; Sinclair, Paul; Harrison, Christine J; Irving, Julie A E

    2017-04-01

    Relapsed acute lymphoblastic leukemia is the most common cause of cancer-related mortality in young people and new therapeutic strategies are needed to improve outcome. Recent studies have shown that heterozygous inactivating mutations in the histone acetyl transferase, CREBBP , are particularly frequent in relapsed childhood acute lymphoblastic leukemia and associated with a hyperdiploid karyotype and KRAS mutations. To study the functional impact of CREBBP haploinsufficiency in acute lymphoblastic leukemia, RNA interference was used to knock down expression of CREBBP in acute lymphoblastic leukemia cell lines and various primagraft acute lymphoblastic leukemia cells. We demonstrate that attenuation of CREBBP results in reduced acetylation of histone 3 lysine 18, but has no significant impact on cAMP-dependent target gene expression. Impaired induction of glucocorticoid receptor targets was only seen in 1 of 4 CREBBP knockdown models, and there was no significant difference in glucocorticoid-induced apoptosis, sensitivity to other acute lymphoblastic leukemia chemotherapeutics or histone deacetylase inhibitors. Importantly, we show that CREBBP directly acetylates KRAS and that CREBBP knockdown enhances signaling of the RAS/RAF/MEK/ERK pathway in Ras pathway mutated acute lymphoblastic leukemia cells, which are still sensitive to MEK inhibitors. Thus, CREBBP mutations might assist in enhancing oncogenic RAS signaling in acute lymphoblastic leukemia but do not alter response to MEK inhibitors. Copyright© Ferrata Storti Foundation.

  4. 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....

  5. Deletions of the long arm of chromosome 5 define subgroups of T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    La Starza, Roberta; Barba, Gianluca; Demeyer, Sofie; Pierini, Valentina; Di Giacomo, Danika; Gianfelici, Valentina; Schwab, Claire; Matteucci, Caterina; Vicente, Carmen; Cools, Jan; Messina, Monica; Crescenzi, Barbara; Chiaretti, Sabina; Foà, Robin; Basso, Giuseppe; Harrison, Christine J; Mecucci, Cristina

    2016-08-01

    Recurrent deletions of the long arm of chromosome 5 were detected in 23/200 cases of T-cell acute lymphoblastic leukemia. Genomic studies identified two types of deletions: interstitial and terminal. Interstitial 5q deletions, found in five cases, were present in both adults and children with a female predominance (chi-square, P=0.012). Interestingly, these cases resembled immature/early T-cell precursor acute lymphoblastic leukemia showing significant down-regulation of five out of the ten top differentially expressed genes in this leukemia group, including TCF7 which maps within the 5q31 common deleted region. Mutations of genes known to be associated with immature/early T-cell precursor acute lymphoblastic leukemia, i.e. WT1, ETV6, JAK1, JAK3, and RUNX1, were present, while CDKN2A/B deletions/mutations were never detected. All patients had relapsed/resistant disease and blasts showed an early differentiation arrest with expression of myeloid markers. Terminal 5q deletions, found in 18 of patients, were more prevalent in adults (chi-square, P=0.010) and defined a subgroup of HOXA-positive T-cell acute lymphoblastic leukemia characterized by 130 up- and 197 down-regulated genes. Down-regulated genes included TRIM41, ZFP62, MAPK9, MGAT1, and CNOT6, all mapping within the 1.4 Mb common deleted region at 5q35.3. Of interest, besides CNOT6 down-regulation, these cases also showed low BTG1 expression and a high incidence of CNOT3 mutations, suggesting that the CCR4-NOT complex plays a crucial role in the pathogenesis of HOXA-positive T-cell acute lymphoblastic leukemia with terminal 5q deletions. In conclusion, interstitial and terminal 5q deletions are recurrent genomic losses identifying distinct subtypes of T-cell acute lymphoblastic leukemia. Copyright© Ferrata Storti Foundation.

  6. 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.

  7. BIM mediates oncogene inactivation-induced apoptosis in multiple transgenic mouse models of acute lymphoblastic leukemia.

    Science.gov (United States)

    Li, Yulin; Deutzmann, Anja; Choi, Peter S; Fan, Alice C; Felsher, Dean W

    2016-05-10

    Oncogene inactivation in both clinical targeted therapies and conditional transgenic mouse cancer models can induce significant tumor regression associated with the robust induction of apoptosis. Here we report that in MYC-, RAS-, and BCR-ABL-induced acute lymphoblastic leukemia (ALL), apoptosis upon oncogene inactivation is mediated by the same pro-apoptotic protein, BIM. The induction of BIMin the MYC- and RAS-driven leukemia is mediated by the downregulation of miR-17-92. Overexpression of miR-17-92 blocked the induction of apoptosis upon oncogene inactivation in the MYC and RAS-driven but not in the BCR-ABL-driven ALL leukemia. Hence, our results provide novel insight into the mechanism of apoptosis upon oncogene inactivation and suggest that induction of BIM-mediated apoptosis may be an important therapeutic approach for ALL.

  8. Metastatic Calcinosis Cutis: A Case in a Child with Acute Pre-B Cell Lymphoblastic Leukemia.

    Science.gov (United States)

    Castanedo-Cázares, Juan Pablo; Reyes-Herrera, Amalia; Hernández-Blanco, Diana; Oros-Ovalle, Cuauhtémoc; Torres-Álvarez, Bertha

    2015-01-01

    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.

  9. Unraveling Glucocorticoid Resistance In MLLrearranged Infant Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    J.A.P. Hagelstein (Jill)

    2014-01-01

    markdownabstract__Abstract__ In the Netherlands, approximately 650 children aged between 0 and 18 years are diagnosed with cancer every year, including ~120 patients suffering from leukemia. Leukemia (Greek for leukos - white, and haima for blood) is a type of cancer characterized by an

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

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    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.

  11. Gum hypertrophy - an unusual presenting feature in a case of precursor T-cell acute lymphoblastic leukemia

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    Lingappa Appaji

    2008-12-01

    Full Text Available Acute lymphoblastic leukemia/lymphoma, the malignant transformation of T-cell or B-cell precursors, is the most common diagnosis in pediatric oncology. Precursor T-cell acute lymphoblastic leukemia/lymphoma commonly affects adolescents, and is associated with mediastinal mass in over half of the cases, with early dissemination to bone marrow, gonads and the central nervous system. We present a rare case of precursor T-cell acute lymphoblastic leukemia/lymphoma with initial oral manifestation, presenting with the unusual features of gum hypertrophy and involvement of upper jaw and palate in a 10-year-old boy. This report discusses the clinical presentation, histopathologic and immunologic features, and diagnosis of this malignancy.

  12. Gum hypertrophy - an unusual presenting feature in a case of precursor T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Premalata, Chennagiri Srinivasamurthy; Madhumati, Davanam Satyanarayana; Lakshmidevi, Vishweshwariah; Pradeep, Rudramurthy; Appaji, Lingappa; Mukherjee, Geetashree

    2008-12-05

    Acute lymphoblastic leukemia/lymphoma, the malignant transformation of T-cell or B-cell precursors, is the most common diagnosis in pediatric oncology. Precursor T-cell acute lymphoblastic leukemia/lymphoma commonly affects adolescents, and is associated with mediastinal mass in over half of the cases, with early dissemination to bone marrow, gonads and the central nervous system. We present a rare case of precursor T-cell acute lymphoblastic leukemia/lymphoma with initial oral manifestation, presenting with the unusual features of gum hypertrophy and involvement of upper jaw and palate in a 10-year-old boy. This report discusses the clinical presentation, histopathologic and immunologic features, and diagnosis of this malignancy.

  13. 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.

  14. HA-1 T TCR T Cell Immunotherapy for the Treating of Patients With Relapsed or Refractory Acute Leukemia After Donor Stem Cell Transplant

    Science.gov (United States)

    2017-11-14

    Acute Biphenotypic Leukemia in Relapse (Diagnosis); Acute Undifferentiated Leukemia in Relapse (Diagnosis); HLA-A*0201 HA-1 Positive Cells Present; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia; Refractory Childhood Acute Myeloid Leukemia

  15. [Effect of metformin addition to an acute lymphoblastic leukemia chemotherapy treatment].

    Science.gov (United States)

    Ramos-Peñafiel, Christian Omar; Martínez-Murillo, Carlos; Santoyo-Sánchez, Adrián; Jiménez-Ponce, Fiacro; Rozen-Fuller, Etta; Collazo-Jaloma, Juan; Olarte-Carrillo, Irma; Martínez-Tovar, Adolfo

    2014-01-01

    Recently it has been reported a benefit effect with the use of metformin in patients with malignant disease. Our objective was to evaluate the effect of adding metformin to chemotherapy regimen over the percentage of early relapse in acute lymphoblastic leukemia. A prospective, longitudinal and experimental study was performed in patients with de novo acute lymphoblastic leukemia enrolled in the Hospital General de México. They were divided in two groups: first group received chemotherapy + metformin (850 mg three times a day); second group only received standard chemotherapy. The sample was randomized 3:1 in favor of the second group. 93 patients were included (73 treated with chemotherapy + metformin and 20 received standard chemotherapy), with 303 ± 53 days of follow-up. Complete remission was higher in the group without metformin (81.3 % [n = 61] versus 70 % [n = 14]), which also presented more patients with relapse (47.9 % versus 25 %). Overall survival at one year was of 68 % and free survival disease was 64 %, without significant differences between groups. Absence of metformin was the only variable of adverse prognostic considered significant (p = 0.55). Cox regression showed that adding metfomin reduced 56 % the risk of relapse. The adding metformin to the treatment of leukemias showed that was useful in our research. However, randomized and double-blind studies must be designed in order to express final recommendations about its use.

  16. Imaging findings of the brain abnormalities in acute lymphoblastic leukemia of children during and after treatment

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyung Joo; Lee, Seung Rho; Park, Dong Woo; Joo, Kyung Bin; Kim, Jang Wook; Hahm, Chang Kok; Kim, Ki Joong; Lee, Hahng [College of Medicine, Hanyang Univ., Seoul (Korea, Republic of)

    2001-09-01

    We evaluated the imaging abnormalities of the brain observed during and after treatment of acute childhood lymphoblastic leukemia. The study group consisted of 30 patients (male : female=19 : 11 ; mean age, 64 months) with acute childhood lymphoblastic leukemia during the previous ten-year period who had undergone prophylaxis of the central nervous system. Irrespective of the CNS symptoms, base-line study of the brain involving CT and follow-up CT or MRI was undertaken more than once. We retrospectively evaluated the imaging findings, methods of treatment, associated CNS symptoms, and the interval between diagnosis and the time at which brain abnormalities were revealed by imaging studies. In 15 (50% ; male : female=9 : 6 ; mean age, 77 months) of 30 patients, brain abnormalities that included brain atrophy (n=9), cerebral infarctions (n=4), intracranial hemorrhage (n=1), mineralizing microangiopathy (n=2), and periventricular leukomalacia (n=3) were seen on follow-up CT or MR images. In four of nine patients with brain atrophy, imaging abnormalities such as periventricular leukomalacia (n=2), infarction (n=1) and microangiopathy (n=1) were demonstrated. Fourteen of the 15 patients underwent similar treatment ; the one excluded had leukemic cells in the CSF. Six patients had CNS symptoms. In the 15 patients with abnormal brain imaging findings, the interval between diagnosis and the demonstration of brain abnormalities was between one month and four years. After the cessation of treatment, imaging abnormalities remained in all patients except one with brain atrophy. Various imaging abnormalities of the brain may be seen during and after the treatment of acute childhood lymphoblastic leukemia and persist for a long time. In children with this condition, the assessment of brain abnormalities requires follow-up study of the brain.

  17. Chimeric Antigen Receptor T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Ciprian Tomuleasa

    2018-02-01

    Full Text Available Chimeric antigen receptor (CAR T-cell technology has seen a rapid development over the last decade mostly due to the potential that these cells may have in treating malignant diseases. It is a generally accepted principle that very few therapeutic compounds deliver a clinical response without treatment-related toxicity, and studies have shown that CAR T-cells are not an exception to this rule. While large multinational drug companies are currently investigating the potential role of CAR T-cells in hematological oncology, the potential of such cellular therapies are being recognized worldwide as they are expected to expand in the patient to support the establishment of the immune memory, provide a continuous surveillance to prevent and/or treat a relapse, and keep the targeted malignant cell subpopulation in check. In this article, we present the possible advantages of using CAR T-cells in treating acute lymphoblastic leukemia, presenting the technology and the current knowledge in their preclinical and early clinical trial use. Thus, this article first presents the main present-day knowledge on the standard of care for acute lymphoblastic leukemia. Afterward, current knowledge is presented about the use of CAR T-cells in cancer immunotherapy, describing their design, the molecular constructs, and the preclinical data on murine models to properly explain the background for their clinical use. Last, but certainly not least, this article presents the use of CAR T-cells for the immunotherapy of B-cell acute lymphoblastic leukemia, describing both their potential clinical advantages and the possible side effects.

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

    Directory of Open Access Journals (Sweden)

    Lee KJ

    2016-08-01

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

  19. Near-haploid and low-hypodiploid acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Safavi, Setareh; Paulsson, Kajsa

    2017-01-01

    Hypodiploidy leukemia (ALL) in both children and adults. It has long been clear by cytogenetic analyses, and recently confirmed by mutational profiling, that these cases may be further subdivided into 2 subtypes: near-haploid ALL...

  20. 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.

  1. Chronic Disseminated Candidiasis Complicated by Immune Reconstitution Inflammatory Syndrome in Child with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Olga Zając-Spychała

    2016-01-01

    Full Text Available Hepatosplenic candidiasis also known as chronic disseminated candidiasis is a rare manifestation of invasive fungal infection typically observed in patients with acute leukemia in prolonged, deep neutropenia. Immune reconstitution inflammatory syndrome (IRIS is an inflammatory disorder triggered by rapid resolution of neutropenia. Diagnosis and treatment of IRIS are still challenging due to a variety of clinical symptoms, lack of certain diagnostic criteria, and no standards of treatment. The diagnosis of IRIS is even more difficult in patients with hematological malignancies complicated by “probable” invasive fungal infection, when fungal pathogen is still uncertain. We report a case of probable hepatic candidiasis in 4-year-old boy with acute lymphoblastic leukemia. Despite proper antifungal therapy, there was no clinical and radiological improvement, so diagnosis of Candida-related IRIS was made and corticosteroid therapy was added to antifungal treatment achieving prompt resolution of infection symptoms.

  2. New immune strategies for the treatment of acute lymphoblastic leukemia: antibodies and chimeric antigen receptors.

    Science.gov (United States)

    Advani, Anjali S

    2013-01-01

    The prognosis of adult acute lymphoblastic leukemia (ALL) remains poor and novel treatment strategies are needed. Antibody-based therapies represent such an approach. ALL cells express various surface antigens that are targets for monoclonal antibodies. This review focuses on 4 major classes of antibody therapy: (1) naked antibodies, (2) T-cell-engaging bispecific single-chain antibodies, (3) immunoconjugates/immunotoxins, and (4) chimeric antigen receptors. Preclinical and clinical data are reviewed. This area of research represents an exciting new approach to help improve the outcome of this disease. Several clinical trials are currently incorporating this therapy in the treatment of newly diagnosed and relapsed adult ALL patients.

  3. The relationship between iron bone marrow stores and response to treatment in pediatric acute lymphoblastic leukemia

    OpenAIRE

    Moafi,Alireza; Ziaie, Mozhdeh; Abedi, Marjan; Rahgozar, Soheila; Reisi, Nahid; NEMATOLLAHI, Pardis; Moafi, Hadi

    2017-01-01

    Abstract Iron is an intracellular element whose accumulation in the body is associated with tissue damage. This study examines the effect of iron on pediatric acute lymphoblastic leukemia (ALL) and its “response to treatment.” At the end of the first year of treatment, bone marrow iron store (BMIS) was evaluated in children with ALL and the relationship between iron store and minimal residual disease was investigated. Moreover, the 3-year disease-free survival (3-DFS) of patients was determin...

  4. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia | Office of Cancer Genomics

    Science.gov (United States)

    Publication Abstract:  Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR-ABL1-positive ALL, alterations of lymphoid transcription factor genes, and a poor outcome. The frequency and spectrum of genetic alterations in Ph-like ALL and its responsiveness to tyrosine kinase inhibition are undefined, especially in adolescents and adults. We performed genomic profiling of 1725 patients with precursor B-cell ALL and detailed genomic analysis of 154 patients with Ph-like ALL.

  5. Severe hypercalcemia: a rare and unusual presentation of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Bahoush, Gholamreza; Miri-Aliabad, Ghasem

    2014-01-01

    Hypercalcemia in children is a medical emergency and often manifests as nonspecific symptoms such as nausea, vomiting, weight loss, and anorexia. Severe hypercalcemia is a rare complication of malignancy in children, while it can be seen in various types of malignant tumors. It is usually associated with significant morbidity and may be severe enough to threaten life. Incidence of hypercalcemia in hematopoietic malignancies including acute lymphoblastic leukemia (ALL) is very rare and unusual, especially as the initial manifestation of the disease. In this paper a 6-year-old boy who had severe hypercalcemia and gastrointestinal symptoms before the onset of common and usual manifestations of ALL is introduced.

  6. Acute Lymphoblastic Leukemia with Infective Endocarditis Presented with Unusual Intracardiac Mass

    Directory of Open Access Journals (Sweden)

    Ali Sadeghpour Tabaei

    2017-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a systemic disease that is presented with different symptoms and signs. Cardiac manifestation is rare in ALL, but it is very important and needs appropriate management. It usually presents as leukemic myocardial infiltration and in the presence of cardiac mass comprehensive evaluation for other etiologies is mandatory. We reported on a 6-year-old boy in remission phase of ALL and large cardiac mass in the right atrium with obscure early symptoms and signs, in whom infective endocarditis (IE was diagnosed and appropriate medical treatment was performed. Because the mass was sustained, surgical resection was considered for the patient.

  7. Isolated gut relapse presenting as chronic diarrhea during maintenance therapy for acute lymphoblastic leukemia.

    Science.gov (United States)

    Bhatti, Anuj; Bansal, Deepak; Vashishta, Rakesh K; Lal, Sadhna B

    2010-08-01

    Ten-year-old boy with acute lymphoblastic leukemia (ALL)-T cell subtype was on MRC UKALL 2003-based chemotherapy. Bone marrow attained remission after induction. After 8 months into maintenance, he presented with chronic diarrhea and weight loss. Search for infective and malabsorptive etiology was unrewarding. Infiltration with leukemic cells was seen in the lamina propria on mucosal biopsies of duodenum and colon. Marrow was in remission. Isolated gut relapse is exceedingly rare. It should be considered in the etiology of chronic diarrhea in patients with ALL, after common causes are excluded.

  8. Steroid-induced Hypertension During Induction Chemotherapy for Acute Lymphoblastic Leukemia in US Children's Hospitals.

    Science.gov (United States)

    Bakk, Ian; Koch, Terah; Stanek, Joseph; O'Brien, Sarah H; Reed, Suzanne

    2018-01-01

    Childhood acute lymphoblastic leukemia achieves excellent cure rates in part due to induction chemotherapy including high dose corticosteroids. Hypertension (HTN) is a known complication of corticosteroids, but incidence and risk factors for steroid-induced HTN are poorly understood. We sought to describe these using a large pediatric health database. Of the 5578 unique patients receiving induction chemotherapy, 14.7% received anti-HTN medications during their initial hospital admission. We found that age below 1 year, obesity, secondary diabetes mellitus, and abnormal glucose were associated with developing steroid-induced HTN. We also found that ICD-9 codes had poor sensitivity for detecting treatment of HTN, suggesting underreporting by physicians.

  9. Etiology and outcome of oral mucosal lesions in children on chemotherapy for acute lymphoblastic leukemia.

    Science.gov (United States)

    Anirudhan, Deepa; Bakhshi, Sameer; Xess, Immaculata; Broor, Shobha; Arya, L S

    2008-01-01

    Microbiological cultures were taken from oral cavity and blood in 100 mucositis episodes in 70 children with acute lymphoblastic leukemia (ALL). Oral mucositis was commonest in neutropenic children during induction chemotherapy. Fungal organisms (n=39) were commonest isolate from mucosa followed by bacteria (n=28). Isolation of organism from oral cavity had no association with those isolated from blood. Herpes serology was positive in 16% episodes compared to 2% of controls. Obtaining cultures from oral lesions is useful in appropriate management of lesions and thereby possibly preventing systemic spread.

  10. Children’s Oncology Group’s 2013 Blueprint for Research: Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Hunger, Stephen P.; Loh, Mignon L.; Whitlock, James A.; Winick, Naomi J.; Carroll, William L.; Devidas, Meenakshi; Raetz, Elizabeth A.

    2014-01-01

    Approximately 90% of the 2,000 children, adolescents, and young adults enrolled each year in Children’s Oncology Group acute lymphoblastic leukemia (ALL) trials will be cured. However, high-risk subsets with significantly inferior survival remain, including infants, newly diagnosed patients with age ≥10 years, white blood count ≥50,000/µl, poor early response or T-cell ALL, and relapsed ALL patients. Effective strategies to improve survival include better risk stratification, optimizing standard chemotherapy and combining targeted therapies with cytotoxic chemotherapy, the latter of which is dependent upon identification of key driver mutations present in ALL. PMID:23255467

  11. The significance of PTEN and AKT aberrations in pediatric T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    Zuurbier, Linda; Petricoin, Emanuel F.; Vuerhard, Maartje J.; Calvert, Valerie; Kooi, Clarissa; Buijs-Gladdines, Jessica G.C.A.M.; Smits, Willem K.; Sonneveld, Edwin; Veerman, Anjo J.P.; Kamps, Willem A.; Horstmann, Martin; Pieters, Rob; Meijerink, Jules P.P.

    2012-01-01

    Background PI3K/AKT pathway mutations are found in T-cell acute lymphoblastic leukemia, but their overall impact and associations with other genetic aberrations is unknown. PTEN mutations have been proposed as secondary mutations that follow NOTCH1-activating mutations and cause cellular resistance to γ-secretase inhibitors. Design and Methods The impact of PTEN, PI3K and AKT aberrations was studied in a genetically well-characterized pediatric T-cell leukemia patient cohort (n=146) treated on DCOG or COALL protocols. Results PTEN and AKT E17K aberrations were detected in 13% and 2% of patients, respectively. Defective PTEN-splicing was identified in incidental cases. Patients without PTEN protein but lacking exon-, splice-, promoter mutations or promoter hypermethylation were present. PTEN/AKT mutations were especially abundant in TAL- or LMO-rearranged leukemia but nearly absent in TLX3-rearranged patients (P=0.03), the opposite to that observed for NOTCH1-activating mutations. Most PTEN/AKT mutant patients either lacked NOTCH1-activating mutations (P=0.006) or had weak NOTCH1-activating mutations (P=0.011), and consequently expressed low intracellular NOTCH1, cMYC and MUSASHI levels. T-cell leukemia patients without PTEN/AKT and NOTCH1-activating mutations fared well, with a cumulative incidence of relapse of only 8% versus 35% for PTEN/AKT and/or NOTCH1-activated patients (P=0.005). Conclusions PI3K/AKT pathway aberrations are present in 18% of pediatric T-cell acute lymphoblastic leukemia patients. Absence of strong NOTCH1-activating mutations in these cases may explain cellular insensitivity to γ-secretase inhibitors. PMID:22491738

  12. Tumor suppressors BTG1 and IKZF1 cooperate during mouse leukemia development and increase relapse risk in B-cell precursor acute lymphoblastic leukemia patients.

    Science.gov (United States)

    Scheijen, Blanca; Boer, Judith M; Marke, René; Tijchon, Esther; van Ingen Schenau, Dorette; Waanders, Esmé; van Emst, Liesbeth; van der Meer, Laurens T; Pieters, Rob; Escherich, Gabriele; Horstmann, Martin A; Sonneveld, Edwin; Venn, Nicola; Sutton, Rosemary; Dalla-Pozza, Luciano; Kuiper, Roland P; Hoogerbrugge, Peter M; den Boer, Monique L; van Leeuwen, Frank N

    2017-03-01

    Deletions and mutations affecting lymphoid transcription factor IKZF1 (IKAROS) are associated with an increased relapse risk and poor outcome in B-cell precursor acute lymphoblastic leukemia. However, additional genetic events may either enhance or negate the effects of IKZF1 deletions on prognosis. In a large discovery cohort of 533 childhood B-cell precursor acute lymphoblastic leukemia patients, we observed that single-copy losses of BTG1 were significantly enriched in IKZF1 -deleted B-cell precursor acute lymphoblastic leukemia ( P =0.007). While BTG1 deletions alone had no impact on prognosis, the combined presence of BTG1 and IKZF1 deletions was associated with a significantly lower 5-year event-free survival ( P =0.0003) and a higher 5-year cumulative incidence of relapse ( P =0.005), when compared with IKZF1 -deleted cases without BTG1 aberrations. In contrast, other copy number losses commonly observed in B-cell precursor acute lymphoblastic leukemia, such as CDKN2A/B, PAX5, EBF1 or RB1 , did not affect the outcome of IKZF1 -deleted acute lymphoblastic leukemia patients. To establish whether the combined loss of IKZF1 and BTG1 function cooperate in leukemogenesis, Btg1 -deficient mice were crossed onto an Ikzf1 heterozygous background. We observed that loss of Btg1 increased the tumor incidence of Ikzf1 +/- mice in a dose-dependent manner. Moreover, murine B cells deficient for Btg1 and Ikzf1 +/- displayed increased resistance to glucocorticoids, but not to other chemotherapeutic drugs. Together, our results identify BTG1 as a tumor suppressor in leukemia that, when deleted, strongly enhances the risk of relapse in IKZF1 -deleted B-cell precursor acute lymphoblastic leukemia, and augments the glucocorticoid resistance phenotype mediated by the loss of IKZF1 function. Copyright© Ferrata Storti Foundation.

  13. 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

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

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    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. Case report of acute lymphoblastic leukemia with multiple soft tissue mass

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Jung Yong; Huh, Kyung Hoe; Yi, Won Jin; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-06-15

    A 15-year-old patient, who had been diagnosed and treated as Burkitt cell type acute lymphoblastic leukemia (ALL-L3) already, visited our department. He complained of gingival enlargement and loosening teeth 1 month ago. The clinical examination revealed anterior open bite, gingival enlargement, and non tender swelling particularly in molar regions of both jaws. Deep periodontal pockets and severe mobility was shown on most of the teeth. The panoramic radiographs showed severe bone destruction and extrusion of the molars. The contrast enhanced CT showed multiple enhanced mass and bone marrow obliteration in both jaws. Chemotherapy was done the swelling was subsided at 1 month later. In conclusion, radiologic findings of leukemia with soft tissue mass, known as chloroma or granulocytic sarcoma, mimic those of lymphoma, so blood test may be needed for the final diagnosis.

  16. The Association Between Motor Skills and Academic Achievement Among Pediatric Survivors of Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Balsamo, Lyn M; Sint, Kyaw J; Neglia, Joseph P; Brouwers, Pim; Kadan-Lottick, Nina S

    2016-04-01

    Assess the association between fine motor (FM) and visual-motor integration (VMI) skills and academic achievement in pediatric acute lymphoblastic leukemia (ALL) survivors. In this 28-site cross-sectional study of 256 children in first remission, a mean of 8.9 ± 2.2 years after treatment for standard-risk precursor-B ALL, validated measures of FM, VMI, reading, math, and intelligence were administered at mean follow-up age of 12.8 ± 2.5 years.   VMI was significantly associated with written math calculation ability (p achievement. These findings suggest that VMI is associated with aspects of math and reading achievement in leukemia survivors. These skills may be amenable to intervention. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. The biology, pathogenesis and clinical aspects of acute lymphoblastic leukemia in children with Down syndrome.

    Science.gov (United States)

    Lee, P; Bhansali, R; Izraeli, S; Hijiya, N; Crispino, J D

    2016-09-01

    Children with Down syndrome (DS) are at a 20-fold increased risk for acute lymphoblastic leukemia (DS-ALL). Although the etiology of this higher risk of developing leukemia remains largely unclear, the recent identification of CRLF2 (cytokine receptor like factor 2) and JAK2 mutations and study of the effect of trisomy of Hmgn1 and Dyrk1a (dual-specificity tyrosine phosphorylation-regulated kinase 1A) on B-cell development have shed significant new light on the disease process. Here we focus on the clinical features, biology and genetics of ALL in children with DS. We review the unique characteristics of DS-ALL on both the clinical and molecular levels and discuss the differences in treatments and outcomes in ALL in children with DS compared with those without DS. The identification of new biological insights is expected to pave the way for novel targeted therapies.

  18. Outcome of Adolescents with Acute Lymphoblastic Leukemia Treated by Pediatrics versus Adults Protocols

    Directory of Open Access Journals (Sweden)

    Abeer Ibrahim

    2014-01-01

    Full Text Available Objective. Several studies showed better outcome in adolescents and young adults with acute lymphoblastic leukemia (ALL treated with pediatrics protocols than similarly aged patients treated with adults protocols, while other studies showed similar outcome of both protocols. We conducted this study to compare the outcome of our pediatrics and adults therapeutic protocols in treatment of adolescents ALL. Patients and Methods. We retrospectively reviewed files of 86 consecutive adolescent ALL patients aged 15–18 years who attended to outpatients clinic from January 2003 to January 2010. 32 out of 86 were treated with pediatrics adopted BFM 90 high risk protocol while 54 were treated with adults adopted BFM protocol. We analyzed the effect of different treatment protocols on achieving complete remission (CR, disease-free survival (DFS, and overall survival (OS. Results. The 2 patients groups have almost similar characteristics. The CR was significantly higher in pediatrics protocol 96% versus 89% (P=0.001. Despite the fact that the toxicity profiles were higher in pediatrics protocol, they were tolerable. Moreover, the pediatrics protocol resulted in superior outcome in EFS 67% versus 39% (P=0.001, DFS 65% versus 41% (P=0.000, and OS 67% versus 45% (P=0.000. Conclusion. Our study’s findings recommend using intensified pediatrics inspired protocol to treat adolescents with acute lymphoblastic leukemia.

  19. Spontaneous perforation of sigmoid colon in a child with acute lymphoblastic leukemia

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    Miolski Jelena

    2017-01-01

    Full Text Available Introduction. Perforation of the sigmoid colon is rare in children and its descriptions in medical literature are infrequent. Case Outline. In a 13-year-old boy with acute lymphoblastic leukemia, a ten-month course of chemotherapy was accompanied by many complications: parasitic infestation (Enterobius vermicularis, lung candidiasis, esophageal candidiasis, steroid diabetes, anaphylactoid reaction to L-asparaginase, febrile neutropenia, mucositis, anemia, thrombocytopenia, enterocolitis, and respiratory distress syndrome. During reinduction treatment, consisting of dexamethasone, vincristine, doxorubicin, and crisantaspase, he complained of abdominal pain and, upon radiographic examination, was found to have pneumoperitoneum. Because of suspicion of abdominal hollow organ perforation, he was subjected to explorative laparotomy, which yielded the diagnosis of perforation of the sigmoid colon. Conclusion. After an extensive review of the published reports on sigmoid perforation, all associated conditions that could possibly induce perforation – such as Hirschsprung’s disease or foreign body – were systematically excluded in our patient. Although typhlitis was the first diagnostic hypothesis, this was excluded by intraoperative findings, histopathology, and perforation site. To the best of our knowledge, this is the first report of a spontaneous perforation of the sigmoid colon in a child with acute lymphoblastic leukemia.

  20. Dexamethasone exposure and asparaginase antibodies affect relapse risk in acute lymphoblastic leukemia

    Science.gov (United States)

    Kawedia, Jitesh D.; Liu, Chengcheng; Pei, Deqing; Cheng, Cheng; Fernandez, Christian A.; Howard, Scott C.; Campana, Dario; Panetta, John C.; Bowman, W. Paul; Evans, William E.; Pui, Ching-Hon

    2012-01-01

    We have previously hypothesized that higher systemic exposure to asparaginase may cause increased exposure to dexamethasone, both critical chemotherapeutic agents for acute lymphoblastic leukemia. Whether interpatient pharmaco-kinetic differences in dexamethasone contribute to relapse risk has never been studied. The impact of plasma clearance of dexamethasone and anti–asparaginase antibody levels on risk of relapse was assessed in 410 children who were treated on a front-line clinical trial for acute lymphoblastic leukemia and were evaluable for all pharmacologic measures, using multivariate analyses, adjusting for standard clinical and biologic prognostic factors. Dexamethasone clearance (mean ± SD) was higher (P = 3 × 10−8) in patients whose sera was positive (17.7 ± 18.6 L/h per m2) versus nega-tive (10.6 ± 5.99 L/h per m2) for anti–asparaginase antibodies. In multivariate analyses, higher dexamethasone clearance was associated with a higher risk of any relapse (P = .01) and of central nervous system relapse (P = .014). Central nervous system relapse was also more common in patients with anti–asparaginase antibodies (P = .019). In conclusion, systemic clearance of dexamethasone is higher in patients with anti–asparaginase antibodies. Lower exposure to both drugs was associated with an increased risk of relapse. PMID:22117041

  1. An early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study.

    Science.gov (United States)

    Bond, Jonathan; Marchand, Tony; Touzart, Aurore; Cieslak, Agata; Trinquand, Amélie; Sutton, Laurent; Radford-Weiss, Isabelle; Lhermitte, Ludovic; Spicuglia, Salvatore; Dombret, Hervé; Macintyre, Elizabeth; Ifrah, Norbert; Hamel, Jean-François; Asnafi, Vahid

    2016-06-01

    Gene expression studies have consistently identified a HOXA-overexpressing cluster of T-cell acute lymphoblastic leukemias, but it is unclear whether these constitute a homogeneous clinical entity, and the biological consequences of HOXA overexpression have not been systematically examined. We characterized the biology and outcome of 55 HOXA-positive cases among 209 patients with adult T-cell acute lymphoblastic leukemia uniformly treated during the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003 and -2005 studies. HOXA-positive patients had markedly higher rates of an early thymic precursor-like immunophenotype (40.8% versus 14.5%, P=0.0004), chemoresistance (59.3% versus 40.8%, P=0.026) and positivity for minimal residual disease (48.5% versus 23.5%, P=0.01) than the HOXA-negative group. These differences were due to particularly high frequencies of chemoresistant early thymic precursor-like acute lymphoblastic leukemia in HOXA-positive cases harboring fusion oncoproteins that transactivate HOXA Strikingly, the presence of an early thymic precursor-like immunophenotype was associated with marked outcome differences within the HOXA-positive group (5-year overall survival 31.2% in HOXA-positive early thymic precursor versus 66.7% in HOXA-positive non-early thymic precursor, P=0.03), but not in HOXA-negative cases (5-year overall survival 74.2% in HOXA-negative early thymic precursor versus 57.2% in HOXA-negative non-early thymic precursor, P=0.44). Multivariate analysis further revealed that HOXA positivity independently affected event-free survival (P=0.053) and relapse risk (P=0.039) of chemoresistant T-cell acute lymphoblastic leukemia. These results show that the underlying mechanism of HOXA deregulation dictates the clinico-biological phenotype, and that the negative prognosis of early thymic precursor acute lymphoblastic leukemia is exclusive to HOXA-positive patients, suggesting that early treatment intensification is currently

  2. Case-control study of childhood acute lymphoblastic leukemia and residential radon exposure.

    Science.gov (United States)

    Lubin, J H; Linet, M S; Boice, J D; Buckley, J; Conrath, S M; Hatch, E E; Kleinerman, R A; Tarone, R E; Wacholder, S; Robison, L L

    1998-02-18

    Several ecologic analyses have shown significant positive associations between mean indoor radon concentrations and risk of leukemia at all ages (acute myeloid leukemia and chronic lymphocytic leukemia) and for children (all leukemia, acute myeloid leukemia, and acute lymphoblastic leukemia [ALL]). As part of an age-matched, case-control study of childhood ALL in the United States, we investigated the association between the incidence of ALL in children under age 15 years and indoor radon exposure. Radon detectors were placed in current and previous homes of subjects where they resided for 6 months or longer. Children were included in analyses if radon measurements covered 70% or more of the 5-year period prior to diagnosis for case subjects (or from birth for case subjects under age 5 years) and the corresponding reference dates for control subjects. Radon levels could be estimated for 97% of the exposure period for the eligible 505 case subjects and 443 control subjects. Mean radon concentration was lower for case subjects (65.4 becquerels per cubic meter [Bqm(-3)]) than for control subjects (79.1 Bqm(-3)). For categories less than 37, 37-73, 74-147, and 148 or more Bqm(-3) of radon exposure, relative risks based on matched case-control pairs were 1.00, 1.22, 0.82, and 1.02, respectively, and were similar to results from an unmatched analysis. There was no association between ALL and radon exposure within subgroups defined by categories of age, income, birth order, birth weight, sex, type of residence, magnetic field exposure, parental age at the subject's birth, parental occupation, or parental smoking habits. In contrast to prior ecologic studies, the results from this analytic study provide no evidence for an association between indoor radon exposure and childhood ALL.

  3. Fasting selectively blocks development of acute lymphoblastic leukemia via leptin-receptor upregulation.

    Science.gov (United States)

    Lu, Zhigang; Xie, Jingjing; Wu, Guojin; Shen, Jinhui; Collins, Robert; Chen, Weina; Kang, Xunlei; Luo, Min; Zou, Yizhou; Huang, Lily Jun-Shen; Amatruda, James F; Slone, Tamra; Winick, Naomi; Scherer, Philipp E; Zhang, Cheng Cheng

    2017-01-01

    New therapeutic approaches are needed to treat leukemia effectively. Dietary restriction regimens, including fasting, have been considered for the prevention and treatment of certain solid tumor types. However, whether and how dietary restriction affects hematopoietic malignancies is unknown. Here we report that fasting alone robustly inhibits the initiation and reverses the leukemic progression of both B cell and T cell acute lymphoblastic leukemia (B-ALL and T-ALL, respectively), but not acute myeloid leukemia (AML), in mouse models of these tumors. Mechanistically, we found that attenuated leptin-receptor (LEPR) expression is essential for the development and maintenance of ALL, and that fasting inhibits ALL development by upregulation of LEPR and its downstream signaling through the protein PR/SET domain 1 (PRDM1). The expression of LEPR signaling-related genes correlated with the prognosis of pediatric patients with pre-B-ALL, and fasting effectively inhibited B-ALL growth in a human xenograft model. Our results indicate that the effects of fasting on tumor growth are cancer-type dependent, and they suggest new avenues for the development of treatment strategies for leukemia.

  4. A case of atypical hemolytic uremic syndrome as an early manifestation of acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Dong Kyun Han

    2010-02-01

    Full Text Available Hemolytic uremic syndrome (HUS is the most common cause of acute renal failure in children younger than 4 years and is characterized by microangiopathic hemolytic anemia, acute renal failure, and thrombocytopenia. HUS associated with diarrheal prodrome is usually caused by Shiga toxin-producing Escherichia coli O157:H7 or by Shigella dysenteriae, which generally has a better outcome. However, atypical cases show a tendency to relapse with a poorer prognosis. HUS has been reported to be associated with acute lymphoblastic leukemia (ALL in children. The characteristics and the mechanisms underlying this condition are largely unknown. In this study, we describe the case of an 11-year-old boy in whom the diagnosis of ALL was preceded by the diagnosis of atypical HUS. Thus, patients with atypical HUS should be diagnosed for the possibility of developing ALL.

  5. Acute Lymphocytic Leukemia

    Science.gov (United States)

    ... al. Clinical manifestations and treatment of acute lymphoblastic leukemia in children. In: Hematology: Basic Principles and Practice. 6th ed. ... National Cancer Institute. http://www.cancer.gov/types/leukemia/patient/child-all-treatment-pdq#section/all. Accessed June 5, ...

  6. 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

  7. GENETIC POLYMORPHISMS OF THE FOLATE METABOLIC PATHWAY IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA. A MOLECULAR STUDY AND A PROPOSAL FOR AN INTERPRETATIVE MODEL.

    OpenAIRE

    Orioli, Elisa

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer accounting for 80% of childhood leukemia. The uncontrolled proliferation of lymphoid progenitors in the bone marrow and the accumulation of malignant lymphoblasts in peripheral blood characterize the disease. The molecular analysis of common genetic alterations in lymphoblastic cells has strongly contributed to the comprehension of ALL pathogenesis. Different gene polymorphisms (most of them SNPs) play an important role in...

  8. 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

  9. 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...

  10. Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Toft, N; Birgens, H; Abrahamsson, J

    2018-01-01

    Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients w...

  11. 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

    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...

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

    DEFF Research Database (Denmark)

    Borst, Louise; Wallerek, Sandra; Dalhoff, Kim

    2011-01-01

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

  13. Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K; Forestier, E; Hellebostad, M

    2010-01-01

    Analysis of 2668 children with acute lymphoblastic leukemia (ALL) treated in two successive Nordic clinical trials (Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-92 and ALL-2000) showed that 75% of all patients are cured by first-line therapy, and 83% are long-term survivors...

  14. 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...

  15. Thrombotic effects of asparaginase in two acute lymphoblastic leukemia protocols (NOPHO ALL-1992 versus NOPHO ALL-2000)

    DEFF Research Database (Denmark)

    Ruud, Ellen; Holmstrøm, Henrik; de Lange, Charlotte

    2006-01-01

    treated according to 2 different asparaginase regimens. The study enrolled 30 children treated for acute lymphoblastic leukemia, and they were divided into 2 groups with respect to asparaginase preparation and protocol (NOPHO ALL-1992 versus NOPHO ALL-2000). The coagulation inhibitors antithrombin...

  16. The Eleventh International Childhood Acute Lymphoblastic Leukemia Workshop Report: Ponte di Legno, Italy, 6-7 May 2009

    DEFF Research Database (Denmark)

    Biondi, A; Baruchel, A; Hunger, S

    2009-01-01

    An international childhood acute lymphoblastic leukemia (ALL)working group was formed during the 27th annual meeting of the International Society of Pediatric Oncology in 1995. Since then, 10 workshops have been held to address many issues that help advance treatment outcome of childhood ALL...

  17. Novel in vivo model of inducible multidrug resistance in acute lymphoblastic leukemia with chromosomal translocation t(4;11)

    Science.gov (United States)

    Acute lymphoblastic leukemia (ALL) with translocation t(4;11) is found in 60-85% of infants with ALL and is classified as high-risk due to the generally poor prognosis for survival. Using the SEM cell line established from a patient with t(4;11) ALL, we evaluated the resistance of these cells to the...

  18. Kinase activity profiling reveals active signal transduction pathways in pediatric acute lymphoblastic leukemia : A new approach for target discovery

    NARCIS (Netherlands)

    van der Sligte, Naomi E.; Scherpen, Frank J. G.; Meeuwsen-de Boer, Tiny G. J.; Lourens, Harm Jan; ter Elst, Arja; Diks, Sander H.; Guryev, Victor; Peppelenbosch, Maikel P.; van Leeuwen, Frank N.; de Bont, Eveline S. J. M.

    Still about 20% of patients with acute lymphoblastic leukemia (ALL) struggle with relapse, despite intensive chemotherapy. We and others have shown that kinase activity profiling is able to give more insights in active signal transduction pathways and point out interesting signaling hubs as well as

  19. Kinase activity profiling reveals active signal transduction pathways in pediatric acute lymphoblastic leukemia: A new approach for target discovery

    NARCIS (Netherlands)

    Sligte, N.E. van der; Scherpen, F.J.; Meeuwsen-de Boer, T.G.; Lourens, H.J.; Elst, A. Ter; Diks, S.H.; Guryev, V.; Peppelenbosch, M.P.; Leeuwen, F.N. van; Bont, E.S. de

    2015-01-01

    Still about 20% of patients with acute lymphoblastic leukemia (ALL) struggle with relapse, despite intensive chemotherapy. We and others have shown that kinase activity profiling is able to give more insights in active signal transduction pathways and point out interesting signaling hubs as well as

  20. Intensification of mercaptopurine/methotrexate maintenance chemotherapy may increase the risk of relapse for some children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Björk, Olle; Glomstein, Anders

    2003-01-01

    by erythrocyte (E) levels of TGN and MTX (including polyglutamates) could improve outcome in childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: A total of 538 children with ALL were randomly assigned to have their oral MP/MTX maintenance therapy adjusted by white cell counts (WBC), E-TGN, and E...

  1. Effects of Chemotherapy on Neurocognitive Function in Children With Acute Lymphoblastic Leukemia: A Critical Review of the Literature

    NARCIS (Netherlands)

    Buizer, A.I.; Sonneville, de L.M.J.; Veerman, A.J.P.

    2009-01-01

    Chemotherapy-only treatment has increasingly become the standard of treatment for childhood acute lymphoblastic leukemia (ALL). The objective of this review is to assess the present state of knowledge of the neurocognitive effects of central nervous system (CNS)-directed chemotherapy in children

  2. Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004

    NARCIS (Netherlands)

    Kamps, W. A.; van der Pal-de Bruin, K. M.; Veerman, A. J. P.; Fiocco, M.; Bierings, M.; Pieters, R.

    The Dutch Childhood Oncology Group (DCOG) has used two treatment strategies for children with acute lymphoblastic leukemia (ALL) based on Pinkel's St Jude Total Therapy or the Berlin-Frankfurt-Munster (BFM) backbone. In four successive protocols, 1734 children were treated. Studies ALL-6 and ALL-9

  3. ATF5 polymorphisms influence ATF function and response to treatment in children with childhood acute lymphoblastic leukemia

    OpenAIRE

    Rousseau, Julie; Gagné, Vincent; Labuda, Malgorzata; Beaubois, Cyrielle; Sinnett, Daniel; Laverdière, Caroline; Moghrabi, Albert; Sallan, Stephen E.; Silverman, Lewis B.; Neuberg, Donna; Kutok, Jeffery L.; Krajinovic, Maja

    2011-01-01

    Asparaginase is a standard and critical component in the therapy of childhood acute lymphoblastic leukemia. Asparagine synthetase (ASNS) and the basic region leucine zipper activating transcription factor 5 (ATF5) and arginosuccinate synthase 1 (ASS1) have been shown to mediate the antileukemic effect of asparaginase and to display variable expression between leukemia cells that are resistant and sensitive to treatment. Fourteen polymorphisms in the regulatory and coding regions of these gene...

  4. Analysis of p16 gene mutations and deletions in childhood acute lymphoblastic leukemias

    Directory of Open Access Journals (Sweden)

    José Alexandre Rodrigues Lemos

    Full Text Available CONTEXT: The p16 tumor suppressor gene encodes a cyclin-dependent kinase 4 inhibitor that blocks cell division during the G1 phase of the cell cycle. Alterations in this gene have been reported for various neoplasia types, including acute lymphoblastic leukemias (ALL, especially T-cell acute lymphoblastic leukemias (ALL. OBJECTIVE: To determine probable alterations in the p16 gene in children with acute lymphoblastic leukemias using the polymerase chain reaction (PCR and direct DNA sequencing and also to analyze event-free survival (EFS. DESIGN: Retrospective study. SETTING: Department of Child Care and Pediatrics, Faculty of Medicine of Ribeirão Preto, Universidade Federal de São Paulo. PARTICIPANTS: Fifty-six children with ALL (mean age 4 years. Forty (71.43% had B-cell and 12 (21.43% had T-cell ALL; 4 (7.1% were biphenotypic. SAMPLE: DNA samples were extracted from bone marrow upon diagnosis and/or relapse. In 2 T-cell cases, DNA from cerebrospinal fluid (CSF was analyzed. MAIN MEASUREMENTS: Deletions or nucleotide substitutions in exons 1, 2 and 3 of the p16 gene were determined by PCR and nucleotide sequencing. Event-free survival was determined by the Kaplan-Meyer and log-rank test for patients carrying normal and altered p16. RESULTS: Deletions in exon 3 were observed in five cases. Abnormal migration in PCR was observed in seven cases for exon 1, six for exon 2, and five for exon 3. Mutations in exon 1 were confirmed by direct DNA sequencing in four cases and in exon 2 in two cases. The Kaplan-Meyer survival curves and the log-rank test showed no significant differences in 5-year EFS between children with normal or altered p16, or between patients with B-ALL carrying normal or altered p16 gene. Patients with T-ALL could not be evaluated via Kaplan-Meier due to the small number of cases. CONCLUSIONS: Our results, particularly regarding deletion frequency, agree with others suggesting that deletions in the p16 are initial events in

  5. Central nervous system involvement in acute lymphoblastic leukemia is mediated by vascular endothelial growth factor.

    Science.gov (United States)

    Münch, Vera; Trentin, Luca; Herzig, Julia; Demir, Salih; Seyfried, Felix; Kraus, Johann M; Kestler, Hans A; Köhler, Rolf; Barth, Thomas F E; Te Kronnie, Geertruy; Debatin, Klaus-Michael; Meyer, Lüder H

    2017-08-03

    In acute lymphoblastic leukemia (ALL), central nervous system (CNS) involvement is a major clinical concern. Despite nondetectable CNS leukemia in many cases, prophylactic CNS-directed conventional intrathecal chemotherapy is required for relapse-free survival, indicating subclinical CNS manifestation in most patients. However, CNS-directed therapy is associated with long-term sequelae, including neurocognitive deficits and secondary neoplasms. Therefore, molecular mechanisms and pathways mediating leukemia-cell entry into the CNS need to be understood to identify targets for prophylactic and therapeutic interventions and develop alternative CNS-directed treatment strategies. In this study, we analyzed leukemia-cell entry into the CNS using a primograft ALL mouse model. We found that primary ALL cells transplanted onto nonobese diabetic/severe combined immunodeficiency mice faithfully recapitulated clinical and pathological features of meningeal infiltration seen in patients with ALL. ALL cells that had entered the CNS and were infiltrating the meninges were characterized by high expression of vascular endothelial growth factor A (VEGF). Although cellular viability, growth, proliferation, and survival of ALL cells were found to be independent of VEGF, transendothelial migration through CNS microvascular endothelial cells was regulated by VEGF. The importance of VEGF produced by ALL cells in mediating leukemia-cell entry into the CNS and leptomeningeal infiltration was further demonstrated by specific reduction of CNS leukemia on in vivo VEGF capture by the anti-VEGF antibody bevacizumab. Thus, we identified a mechanism of ALL-cell entry into the CNS, which by targeting VEGF signaling may serve as a novel strategy to control CNS leukemia in patients, replacing conventional CNS-toxic treatment. © 2017 by The American Society of Hematology.

  6. Acute respiratory infections in children and adolescents with acute lymphoblastic leukemia.

    Science.gov (United States)

    Hakim, Hana; Dallas, Ronald; Zhou, Yinmei; Pei, Dequing; Cheng, Cheng; Flynn, Patricia M; Pui, Ching-Hon; Jeha, Sima

    2016-03-01

    Knowledge regarding the incidence, clinical course, and impact of respiratory viral infections in children with acute lymphoblastic leukemia (ALL) is limited. A retrospective cohort of patients with newly diagnosed ALL who were treated on the Total Therapy XVI protocol at St Jude Children's Research Hospital between 2007 and 2011 was evaluated. Of 223 children, 95 (43%) developed 133 episodes of viral acute respiratory illness (ARI) (incidence, 1.1 per 1000 patient-days). ARI without viral etiology was identified in 65 patients (29%) and no ARI was detected in 63 patients (28%). There were no significant associations noted between race, sex, age, or ALL risk group and the development of ARI. Children receiving induction chemotherapy were found to be at the highest risk of viral ARI (incidence, 2.3 per 1000 patient-days). Influenza virus was the most common virus (38%) followed by respiratory syncytial virus (33%). Of 133 episodes of viral ARI, 61% of patients were hospitalized, 26% experienced a complicated course, 80% had their chemotherapy delayed, and 0.7% of patients died. Twenty-four patients (18%) developed viral lower respiratory tract infections (LRTI), 5 of whom (21%) had complications. Patients with viral LRTI had a significantly lower nadir absolute lymphocyte count; were sicker at the time of presentation; and were more likely to have respiratory syncytial virus, to be hospitalized, and to have their chemotherapy delayed for longer compared with those with viral upper respiratory tract infections. Despite the low incidence of viral ARI in children with ALL, the associated morbidity, mortality, and delay in chemotherapy remain clinically significant. Viral LRTI was especially associated with high morbidity requiring intensive care-level support. Cancer 2016;122:798-805. © 2015 American Cancer Society. © 2015 American Cancer Society.

  7. IKAROS Gene Deleted B-Cell Acute Lymphoblastic Leukemia in Mexican Mestizos: Observations in Seven Patients and a Short Review of the Literature.

    Science.gov (United States)

    Ruiz-Delgado, Guillermo José; Cantero-Fortiz, Yahveth; León-Peña, Andrés Aurelio; León-González, Mónica; Nuñez-Cortés, Ana Karen; Ruiz-Argüelles, Guillermo José

    2016-01-01

    In B-cell acute lymphoblastic leukemia, one of the most frequent cytogenetic alterations is the presence of the Philadelphia chromosome. Recently, newly identified genetic alterations have been studied, among them the IKZF1 deletion. IKZF1 encodes IKAROS, a zinc finger protein that plays an important role in hematopoiesis involving the regulation process of adhesion, cellular migration, and as a tumor suppressor. We aimed to study the impact of IKAROS deletion in the evolution and prognosis of B-cell acute lymphoblastic leukemia. At a single center we prospectively studied patients diagnosed with B-cell acute lymphoblastic leukemia and screened for IKZF1 deletion using the multiplex ligation-dependent probe amplification method. We did a descriptive analysis of patients positive for the IKZF1 deletion to determine its impact on the evolution of the disease and survival rate. Between 2010 and 2015, 16 Mexican mestizo patients with B-cell acute lymphoblastic leukemia were prospectively screened for IKZF1 deletion; seven (43%) were positive and were included for further analysis. The age range of patients was 13-60 years; six were males and one female. All cases had type B acute lymphoblastic leukemia. Of the seven patients, two died, three were lost to follow-up, and two continue in complete remission with treatment. Results are worse than those in a group of patients with non-mutated IKAROS B-cell acute lymphoblastic leukemia previously studied in our center. Although this is a small sample, the presence of IKAROS deletion in acute lymphoblastic leukemia patients could represent a poor-prognosis marker and was probably related to therapy failure. It is also possible that this variant of leukemia may be more prevalent in Mexico. More studies are needed to define the role of IKZF1 deletion in acute lymphoblastic leukemia and the real prevalence of the disease in different populations.

  8. Hyper-CVAD plus nelarabine in newly diagnosed adult T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma.

    Science.gov (United States)

    Abaza, Yasmin; M Kantarjian, Hagop; Faderl, Stefan; Jabbour, Elias; Jain, Nitin; Thomas, Deborah; Kadia, Tapan; Borthakur, Gautam; D Khoury, Joseph; Burger, Jan; Wierda, William; O'Brien, Susan; Konopleva, Marina; Ferrajoli, Alessandra; Kebriaei, Partow; Dabaja, Bouthaina; Kornblau, Steven; Alvarado, Yesid; Daver, Naval; Pemmaraju, Naveen; Bose, Prithviraj; Thompson, Philip; Al Azzawi, Hind; Kelly, Mary; Garris, Rebecca; Jain, Preetesh; Garcia-Manero, Guillermo; Cortes, Jorge; Ravandi, Farhad

    2018-01-01

    Nelarabine, a water soluble prodrug of 9-β-D-arabinofuranosylguanine (ara-G), is a T-cell specific purine nucleoside analogue. Given its activity in relapsed and refractory T acute lymphoblastic leukemia (T-ALL) and T lymphoblastic lymphoma (T-LBL), we sought to define its role in the frontline treatment of adult patients. Therefore, we conducted a single arm phase 2 study to determine the safety and efficacy of nelarabine in combination with hyper-CVAD in newly diagnosed patients. For induction/consolidation, patients received eight cycles of hyper-CVAD alternating with high-dose methotrexate and cytarabine plus two cycles of nelarabine given at a dose of 650 mg/m2 intravenously daily for 5 days. This was followed by thirty months of POMP maintenance chemotherapy with two additional cycles of nelarabine given instead of cycles 6 and 7 of POMP maintenance. Sixty-seven patients, including 40 with T-ALL and 26 with T-LBL, were enrolled. Complete response rates in both T-ALL and T-LBL were 87% and 100% respectively. Grade 3 to 4 neurotoxic adverse events were reported in 5 patients. There were 21 relapses (31%) including 2 after allogeneic stem cell transplantation. Median duration of follow-up was 42.5 months. The 3-year complete remission duration (CRD) and overall survival (OS) rates were 66% and 65%, respectively. Compared to our historic hyper-CVAD data, there was no survival benefit with the addition of nelarabine. In conclusion, hyper-CVAD plus nelarabine was well tolerated and active in the frontline treatment of adult T-ALL/LBL patients. © 2017 Wiley Periodicals, Inc.

  9. 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...

  10. Hypergranular acute lymphoblastic leukemia (ALL). Report of a case and review of the literature.

    Science.gov (United States)

    Schwarzinger, I; Födinger, M; Scherrer, R; Wolzt, M; Mannhalter, C; Speiser, W

    1993-12-01

    We report a case of adult acute lymphoblastic leukemia (ALL) with myeloid-like hypergranulation of blast cells. Like most of the "granular" ALLs described in the literature, the blast cells had L2 morphology and exhibited a common-ALL immunologic phenotype. The clinical findings at diagnosis were unremarkable. Cytogenetic analysis showed a 46XY karyotype. Molecular genetic analysis revealed T-cell receptor (TCR) gamma and immunoglobulin heavy chain rearrangements; no rearrangement was found at the TCR beta gene locus. The polymerase chain reaction (PCR) for the BCR-ABL translocation was negative. The clinical course of the patient was uncomplicated. On standard ALL treatment protocol he achieved complete remission (CR) within 4 weeks, and he is currently disease free 8 months after diagnosis. The case contributes well-documented data to the characterization of adult "granular" ALL, with special regard to changes at the molecular genetic level.

  11. Dependent generalized Dirichlet process priors for the analysis of acute lymphoblastic leukemia.

    Science.gov (United States)

    Barcella, William; De Iorio, Maria; Favaro, Stefano; Rosner, Gary L

    2017-09-06

    We propose a novel Bayesian nonparametric process prior for modeling a collection of random discrete distributions. This process is defined by including a suitable Beta regression framework within a generalized Dirichlet process to induce dependence among the discrete random distributions. This strategy allows for covariate dependent clustering of the observations. Some advantages of the proposed approach include wide applicability, ease of interpretation, and availability of efficient MCMC algorithms. The motivation for this work is the study of the impact of asparginage metabolism on lipid levels in a group of pediatric patients treated for acute lymphoblastic leukemia. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Body composition and phase angle in Russian children in remission from acute lymphoblastic leukemia

    Science.gov (United States)

    Tseytlin, G. Ja; Khomyakova, I. A.; Nikolaev, D. V.; Konovalova, M. V.; Vashura, A. Yu; Tretyak, A. V.; Godina, E. Z.; Rudnev, S. G.

    2010-04-01

    Elevated degree of body fatness and changes in other body composition parameters are known to be common effects of treatment for acute lymphoblastic leukemia (ALL) in children. In order to study peculiarities of somatic growth and development in ALL survivors, we describe the results of BIA body composition analysis of 112 boys and 108 girls aged 5-18 years in remission from ALL (remission time range 1-13 years) compared to data from the same number of age- and sex-matched healthy controls (n=220). Detrimental effect on height in ALL boys was observed, whereas girls experienced additional weight gain compared to healthy subjects. In ALL patients, resistance, body fat, and percent body fat were significantly increased. The reactance, phase angle, absolute and relative values of skeletal muscle and body cell mass were significantly decreased. Principal component analysis revealed an early prevalence of adiposity traits in the somatic growth and development of ALL girls compared to healthy controls.

  13. Central Venous Catheters and Bloodstream Infection During Induction Therapy in Children With Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Bergmann, Kristin; Hasle, Henrik; Asdahl, Peter

    2016-01-01

    treated at 3 pediatric centers in Denmark between 2008 and 2014. A total of 136 patients were followed from initial CVC placement until first BSI, CVC removal, death, or day 28, whichever occurred first. Thirty-nine BSIs were detected, of which 67% were gram-positive infections, and 59% met the criteria......The purpose of the study was to assess the risk of firsttime bloodstream infection (BSI) according to type of central venous catheter (CVC) during induction therapy in children with acute lymphoblastic leukemia (ALL). Patients eligible for our analysis were all newly diagnosed children with ALL...... for being CVC associated. The 28-day cumulative incidence of BSI was similar in 77 patients with a nontunneled CVC (28%; 95% confidence interval, 19%-40%) and in 59 patients with a tunneled CVC with external lines (TE) (33%; 95% confidence interval, 23%-47%). Subgroup analyses showed that gram...

  14. Population Analysis of Pharmacogenetic Polymorphisms Related to Acute Lymphoblastic Leukemia Drug Treatment

    Directory of Open Access Journals (Sweden)

    Marcela A. Chiabai

    2012-01-01

    Full Text Available This study aimed to evaluate in the Brazilian population, the genotypes and population frequencies of pharmacogenetic polymorphisms involved in the response to drugs used in treatment of acute lymphoblastic leukemia (ALL, and to compare the data with data from the HapMap populations. There was significant differentiation between most population pairs, but few associations between genetic ancestry and SNPs in the Brazilian population were observed. AMOVA analysis comparing the Brazilian population to all other populations retrieved from HapMap pointed to a genetic proximity with the European population. These associations point to preclusion of the use of genetic ancestry as a proxy for predicting drug response. In this way, any study aiming to correlate genotype with drug response in the Brazilian population should be based on pharmacogenetic SNP genotypes.

  15. On a case of multifocal osteonecrosis in a patient suffering from acute lymphoblastic leukemia.

    Science.gov (United States)

    Solarino, Giuseppe; Scialpi, Lorenzo; Bruno, Marco; De Cillis, Berenice

    2008-09-01

    The Authors describe the case of a 14-year-old girl who developed a multifocal osteonecrosis (ON), after treatment with chemotherapy and corticosteroids for acute lymphoblastic leukemia (ALL). She came to our attention about 6 months after the beginning of treatment complaining of pain in her left knee and later in both hips and shoulders. Radiography and MRI confirmed the presence of avascular ON at all these sites. The patient underwent bilateral total hip arthroplasty, which was still functioning well at the last follow-up visits at 5 years, and at 5 years and 4 months. ON is increasingly recognized as a complication of the treatment of cancer in children and adolescents, and as patients now frequently survive ALL into adulthood, orthopedists will be increasingly called on to manage this complication affecting multiple joints in children and young adults.

  16. Genetic heterogeneity of RPMI-8402, a T-acute lymphoblastic leukemia cell line.

    Science.gov (United States)

    Stoczynska-Fidelus, Ewelina; Piaskowski, Sylwester; Pawlowska, Roza; Szybka, Malgorzata; Peciak, Joanna; Hulas-Bigoszewska, Krystyna; Winiecka-Klimek, Marta; Rieske, Piotr

    2016-01-01

    Thorough examination of genetic heterogeneity of cell lines is uncommon. In order to address this issue, the present study analyzed the genetic heterogeneity of RPMI-8402, a T-acute lymphoblastic leukemia (T-ALL) cell line. For this purpose, traditional techniques such as fluorescence in situ hybridization and immunocytochemistry were used, in addition to more advanced techniques, including cell sorting, Sanger sequencing and massive parallel sequencing. The results indicated that the RPMI-8402 cell line consists of several genetically different cell subpopulations. Furthermore, massive parallel sequencing of RPMI-8402 provided insight into the evolution of T-ALL carcinogenesis, since this cell line exhibited the genetic heterogeneity typical of T-ALL. Therefore, the use of cell lines for drug testing in future studies may aid the progress of anticancer drug research.

  17. 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...... methylation as a complement to current diagnostic methods. A secondary aim was to gain insight into the functional role of DNA methylation in ALL. RESULTS: We used the methylation status of ~450,000 CpG sites in 546 well-characterized patients with T-ALL or seven recurrent B-cell precursor ALL subtypes...... methylation classification to screen for subtype membership of 210 patients with undefined karyotype (normal or no result) or non-recurrent cytogenetic aberrations ('other' subtype). Nearly half (n = 106) of the patients lacking cytogenetic subgrouping displayed highly similar methylation profiles...

  18. Primary laryngeal manifestation in precursor T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Wang, Lin; Ma, Yan; Chen, Bobin; Tang, Feng; Xu, Xiaoping; Lin, Guowei

    2015-02-01

    Primary involvement of the larynx in non-Hodgkin's lymphoma (NHL) is rare. Early symptoms are non-specific and thus, it is difficult to diagnose. In the present study, the case of a 52 year-old male with hoarseness due to diffuse T-cell lymphoma as the first manifestation of precursor T-cell acute lymphoblastic leukemia is presented. Subsequent to treatment with three cycles of the etoposide and cytosine arabinoside (EA) and one cycle of the EA+L-asp chemotherapy regimens, the patient achieved complete remission. A series of consolidation therapy courses were performed subsequently. At present, the patient remains disease-free, indicating that the treatment was effective. Primary involvement of the larynx in NHL is rare. Symptoms in the early stage are subtle and non-specific and thus, diagnosis is difficult to establish. This type of tumor requires special diagnostic and therapeutic attention.

  19. OSTEOPOROSIS IN A SEVENTH YEAR OLD BOY WITH ACUTE LYMPHOBLASTIC LEUKEMIA (Case Report

    Directory of Open Access Journals (Sweden)

    H Salim

    2013-09-01

    Full Text Available Osteoporosis in children is rare and usually secondary to an underlying disease process whose diagnosis may be difficult to detect. It can be a manifestation of acute lymphoblastic leukemia (ALL. About a-quarters of children with ALL will have signs and symptoms of osteoporosis. We report the case of a seventh-year-old boy with back pain. His antero-posterior pelvic radiograph showed the osteoporotic bone. The bone age study revealed six-year-old bone. Review of peripheral blood smear showed normochromic anemia with thrombocytopenia. Immunophenotyping of peripheral blood revealed no dominant marker was seen, but the bone marrow aspiration confirms the diagnosis of ALL (L2.

  20. Extramedullary Relapse of Acute Lymphoblastic Leukemia Presenting as Abnormal Uterine Bleeding: A Case Report.

    Science.gov (United States)

    Robillard, Diana T; Kutny, Matthew A; Chewning, Joseph H; Arbuckle, Janeen L

    2017-06-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Relapse of ALL occurs in 15%-20% of patients, with 2%-6% occurring exclusively in extramedullary sites. Relapse of ALL in gynecologic organs is extremely rare. We present a case of a 12-year-old girl with a history of ALL who was referred to the pediatric gynecology clinic with abnormal uterine bleeding. She was determined to have an extramedullary uterine relapse of her ALL. Abnormal uterine bleeding in the setting of childhood malignancy is a frequent reason for consultation to pediatric and adolescent gynecology services. This bleeding is commonly attributed to thrombocytopenia due to bone marrow suppressive chemotherapeutic agents. However, as shown in this report, abnormal uterine bleeding might be a manifestation of an extramedullary relapse. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  1. Association of clinical trial enrollment and survival using contemporary therapy for pediatric acute lymphoblastic leukemia.

    Science.gov (United States)

    Moke, Diana J; Oberley, Matthew J; Bhojwani, Deepa; Parekh, Chintan; Orgel, Etan

    2018-02-01

    While early studies reported superior survival for cancer patients enrolled on clinical trials, recent findings are inconclusive. We investigated the association between enrollment on contemporary trials and event-free survival (EFS) in pediatric B-cell acute lymphoblastic leukemia (B-ALL). In a retrospective cohort of 274 children (1-21 years) treated for B-ALL from 2008 to 2015, 55.5% enrolled with no disparity in enrollment by age, sex, or ethnicity. Three-year EFS was similar for enrolled and not enrolled patients (90.1% [95% CI, 82.5-94.5] versus 86.5% [95% CI, 77.7-92.0]). Clinical trial enrollment did not affect pediatric B-ALL survival, albeit in a limited-size cohort treated at a single academic institution. © 2017 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    Vilchis-Ordoñez, Armando; Contreras-Quiroz, Adriana; Dorantes-Acosta, Elisa; Reyes-López, Alfonso; Quintela-Nuñez del Prado, Henry Martin; Venegas-Vázquez, Jorge; Mayani, Hector; Ortiz-Navarrete, Vianney; López-Martínez, Briceida; Pelayo, Rosana

    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 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. PMID:26090405

  3. Cytogenetic study in a mentally retarded child with Bloom syndrome and acute lymphoblastic leukemia.

    Science.gov (United States)

    Werner-Favre, C; Wyss, M; Cabrol, C; Félix, F; Guenin, R; Laufer, D; Engel, E

    1984-06-01

    Bloom syndrome (BS) was diagnosed in a 7-year-old boy during hospitalization for acute lymphoblastic leukemia (ALL). The patient had most of the signs of BS along with some atypical manifestations: absence of telangiectases, obesity, and moderate mental retardation. Results of the cytogenetic studies were fully consistent with the diagnosis of BS: the occurrence of quadriradial figures and a very high incidence of sister-chromatid exchanges (SCE). This child's ALL was of non-B, non-T type with the presence, at the time of diagnosis, of a marrow clone including two markers. A Yq - chromosome was detected in about 10% of PHA-stimulated lymphocytes but neither in bone marrow cells nor in skin fibroblasts. This case is the fifth instance of ALL out of 104 registered cases of BS.

  4. Recurrence of acute lymphoblastic leukemia manifesting as serous retinal detachments and optic disc swelling.

    Science.gov (United States)

    Yabas Kiziloglu, Ozge; Mestanoglu, Mert; Totuk Gedar, Ozgun Melike; Adiguzel, Cafer; Toygar, Okan

    2017-07-15

    The aim of this case report is to describe a patient with acute lymphoblastic leukemia (ALL) who developed bilateral serous retinal detachments and unilateral optic disc swelling. A 23-year-old woman with ALL presented to the ophthalmology clinic with bilateral subacute visual loss. Ophthalmologic examination revealed bilateral serous retinal detachments and unilateral optic disc swelling. Magnetic resonance imaging for differential diagnosis was inconclusive; however, cerebrospinal fluid sampling demonstrated leukemic involvement of the central nervous system. The patient's vision improved and fundus findings resolved with the institution of systemic and intrathecal chemotherapy. Serous retinal detachment and optic disc swelling are unusual ocular manifestations of ALL. They may occur due to leukemic infiltration of ocular structures and may indicate extramedullary recurrence of the disease. Early recognition and treatment is crucial to improve prognosis.

  5. 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.

  6. RBP2 Promotes Adult Acute Lymphoblastic Leukemia by Upregulating BCL2.

    Directory of Open Access Journals (Sweden)

    Xiaoming Wang

    Full Text Available Despite recent increases in the cure rate of acute lymphoblastic leukemia (ALL, adult ALL remains a high-risk disease that exhibits a high relapse rate. In this study, we found that the histone demethylase retinoblastoma binding protein-2 (RBP2 was overexpressed in both on-going and relapse cases of adult ALL, which revealed that RBP2 overexpression was not only involved in the pathogenesis of ALL but that its overexpression might also be related to relapse of the disease. RBP2 knockdown induced apoptosis and attenuated leukemic cell viability. Our results demonstrated that BCL2 is a novel target of RBP2 and supported the notion of RBP2 being a regulator of BCL2 expression via directly binding to its promoter. As the role of RBP2 in regulating apoptosis was confirmed, RBP2 overexpression and activation of BCL2 might play important roles in ALL development and progression.

  7. Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia

    Science.gov (United States)

    Roberts, Kathryn G.; Morin, Ryan D.; Zhang, Jinghui; Hirst, Martin; Zhao, Yongjun; Su, Xiaoping; Chen, Shann-Ching; Payne-Turner, Debbie; Churchman, Michelle; Harvey, Richard C.; Chen, Xiang; Kasap, Corynn; Yan, Chunhua; Becksfort, Jared; Finney, Richard P.; Teachey, David T.; Maude, Shannon L.; Tse, Kane; Moore, Richard; Jones, Steven; Mungall, Karen; Birol, Inanc; Edmonson, Michael N.; Hu, Ying; Buetow, Kenneth E.; Chen, I-Ming; Carroll, William L.; Wei, Lei; Ma, Jing; Kleppe, Maria; Levine, Ross L.; Garcia-Manero, Guillermo; Larsen, Eric; Shah, Neil P.; Devidas, Meenakshi; Reaman, Gregory; Smith, Malcolm; Paugh, Steven W.; Evans, William E.; Grupp, Stephan A.; Jeha, Sima; Pui, Ching-Hon; Gerhard, Daniela S.; Downing, James R.; Willman, Cheryl L.; Loh, Mignon; Hunger, Stephen P.; Marra, Marco; Mullighan, Charles G.

    2012-01-01

    SUMMARY Genomic profiling has identified a subtype of high-risk B-progenitor acute lymphoblastic leukemia (B-ALL) with alteration of IKZF1, a gene expression profile similar to BCR-ABL1-positive ALL and poor outcome (Ph-like ALL). The genetic alterations that activate kinase signaling in Ph-like ALL are poorly understood. We performed transcriptome and whole genome sequencing on 15 cases of Ph-like ALL, and identified rearrangements involving ABL1, JAK2, PDGFRB, CRLF2 and EPOR, activating mutations of IL7R and FLT3, and deletion of SH2B3, which encodes the JAK2 negative regulator LNK. Importantly, several of these alterations induce transformation that is attenuated with tyrosine kinase inhibitors, suggesting the treatment outcome of these patients may be improved with targeted therapy. PMID:22897847

  8. [Treatment of childhood acute lymphoblastic leukemia in a community hospital of the state of Veracruz].

    Science.gov (United States)

    Verduzco-Rodríguez, L; Ibarra-Colado, J

    1998-01-01

    To describe the results of treatment of 36 consecutive children with acute lymphoblastic leukemia attending a second level community hospital in the Mexican State of Veracruz. They were from families with very poor resources seen free of charge. Most (75%) were high risk cases. The most common high risk factors were an age outside the range of 2 to 9 years (53%), a WBC count above 50 thousand/microL (36%) and an L-2 lymphocyte morphology (39%). Disease-free survival was 64% at 36 months whereas event-free survival was 47% at 36 months which are low in comparison with the data in the literature. We believe we were able to obtain good results in the treatment of our leukemic cases which was not only a mostly high risk group but also had to contend with poor nutritional, cultural and socioeconomic conditions and with disease-related factors present in their communities.

  9. Acute lymphoblastic leukemia in idiopathic refractory sideroblastic anemia: evidence for a common lymphoid and myeloid progenitor cell.

    Science.gov (United States)

    Barton, J C; Conrad, M E; Parmley, R T

    1980-01-01

    Acute leukemia of myeloblastic or erythroblastic morphology occasionally occurs as a complication of idiopathic refractory sideroblastic anemia, but the development of acute lymphoblastic leukemia has not been previously reported in these cases. A patient with idiopathic refractory sideroblastic anemia is described in whom acute lymphoblastic leukemia occurred. The leukemic cells were characterized by typical lymphoblastic morphology on Wright's stain, periodic acid-Schiff-positive cytoplasmic clumps, elevated levels of deoxynucleotidyl transferase (143 units/10(8) cells), high numbers of specific glucocorticoid binding sites (16,845 sites/cell, Kd = 5.40 x 10(-9) M), non-B, non-T cell immunologic characteristics and clinical responsiveness to therapy with vincristine, prednisone, and methotrexate. Ultrastructural studies of the lymphoblasts identified ferruginous material in lysosomes and occasional mitochondria similar to but less abundant than that seen in abnormal sideroblasts. The concurrence of these two disorders supports the theory that in humans both lymphoid and myeloid cell lines arise from a common pluripotent stem cell.

  10. Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    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.

  11. PTPRG inhibition by DNA methylation and cooperation with RAS gene activation in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Xiao, Jianqiao; Lee, Seung-Tae; Xiao, Yuanyuan; Ma, Xiaomei; Houseman, E Andres; Hsu, Ling-I; Roy, Ritu; Wrensch, Margaret; de Smith, Adam J; Chokkalingam, Anand; Buffler, Patricia; Wiencke, John K; Wiemels, Joseph L

    2014-09-01

    While the cytogenetic and genetic characteristics of childhood acute lymphoblastic leukemias (ALL) are well studied, less clearly understood are the contributing epigenetic mechanisms that influence the leukemia phenotype. Our previous studies and others identified gene mutation (RAS) and DNA methylation (FHIT) to be associated with the most common cytogenetic subgroup of childhood ALL, high hyperdiploidy (having five more chromosomes). We screened DNA methylation profiles, using a genome-wide high-dimension platform of 166 childhood ALLs and 6 normal pre-B cell samples and observed a strong association of DNA methylation status at the PTPRG locus in human samples with levels of PTPRG gene expression as well as with RAS gene mutation status. In the 293 cell line, we found that PTPRG expression induces dephosphorylation of ERK, a downstream RAS target that may be critical for mutant RAS-induced cell growth. In addition, PTPRG expression is upregulated by RAS activation under DNA hypomethylating conditions. An element within the PTPRG promoter is bound by the RAS-responsive transcription factor RREB1, also under hypomethylating conditions. In conclusion, we provide evidence that DNA methylation of the PTPRG gene is a complementary event in oncogenesis induced by RAS mutations. Evidence for additional roles for PTPR family member genes is also suggested. This provides a potential therapeutic target for RAS-related leukemias as well as insight into childhood ALL etiology and pathophysiology. © 2014 UICC.

  12. Phase I/II study of the hypoxia-activated prodrug PR104 in refractory/relapsed acute myeloid leukemia and acute lymphoblastic leukemia.

    Science.gov (United States)

    Konopleva, Marina; Thall, Peter F; Yi, Cecilia Arana; Borthakur, Gautam; Coveler, Andrew; Bueso-Ramos, Carlos; Benito, Juliana; Konoplev, Sergej; Gu, Yongchuan; Ravandi, Farhad; Jabbour, Elias; Faderl, Stefan; Thomas, Deborah; Cortes, Jorge; Kadia, Tapan; Kornblau, Steven; Daver, Naval; Pemmaraju, Naveen; Nguyen, Hoang Q; Feliu, Jennie; Lu, Hongbo; Wei, Caimiao; Wilson, William R; Melink, Teresa J; Gutheil, John C; Andreeff, Michael; Estey, Elihu H; Kantarjian, Hagop

    2015-07-01

    We previously demonstrated vast expansion of hypoxic areas in the leukemic microenvironment and provided a rationale for using hypoxia-activated prodrugs. PR104 is a phosphate ester that is rapidly hydrolyzed in vivo to the corresponding alcohol PR-104A and further reduced to the amine and hydroxyl-amine nitrogen mustards that induce DNA cross-linking in hypoxic cells under low oxygen concentrations. In this phase I/II study, patients with relapsed/refractory acute myeloid leukemia (n=40) after 1 or 2 prior treatments or acute lymphoblastic leukemia (n=10) after any number of prior treatments received PR104; dose ranged from 1.1 to 4 g/m(2). The most common treatment-related grade 3/4 adverse events were myelosuppression (anemia 62%, neutropenia 50%, thrombocytopenia 46%), febrile neutropenia (40%), infection (24%), and enterocolitis (14%). Ten of 31 patients with acute myeloid leukemia (32%) and 2 of 10 patients with acute lymphoblastic leukemia (20%) who received 3 g/m(2) or 4 g/m(2) had a response (complete response, n=1; complete response without platelet recovery, n=5; morphological leukemia-free state, n=6). The extent of hypoxia was evaluated by the hypoxia tracer pimonidazole administered prior to a bone marrow biopsy and by immunohistochemical assessments of hypoxia-inducible factor alpha and carbonic anhydrase IX. A high fraction of leukemic cells expressed these markers, and PR104 administration resulted in measurable decrease of the proportions of hypoxic cells. These findings indicate that hypoxia is a prevalent feature of the leukemic microenvironment and that targeting hypoxia with hypoxia-activated prodrugs warrants further evaluation in acute leukemia. The trial is registered at clinicaltrials.gov identifier: 01037556. Copyright© Ferrata Storti Foundation.

  13. EFFECTS OF A COMBINED AEROBIC AND STRENGTH TRAINING PROGRAM IN YOUTH PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Maria Beatriz Perondi

    2012-09-01

    Full Text Available Cure rates of youth with Acute Lymphoblastic Leukemia (ALL have increased in the past decades, but survivor's quality of life and physical fitness has become a growing concern. Although previous reports showed that resistance training is feasible and effective, we hypothesized that a more intense exercise program would also be feasible, but more beneficial than low- to moderate-intensity training programs. We aimed to examine the effects of an exercise program combining high-intensity resistance exercises and moderate-intensity aerobic exercises in young patients undergoing treatment for ALL. A quasi-experimental study was conducted. The patients (n = 6; 5-16 years of age underwent a 12-week intra-hospital training program involving high-intensity strength exercises and aerobic exercise at 70% of the peak oxygen consumption. At baseline and after 12 weeks, we assessed sub-maximal strength (10 repetition-maximum, quality of life and possible adverse effects. A significant improvement was observed in the sub maximal strength for bench press (71%, lat pull down (50%, leg press (73% and leg extension (64% as a result of the training (p < 0.01. The parents' evaluations of their children's quality of life revealed an improvement in fatigue and general quality of life, but the children's self-reported quality of life was not changed. No adverse effects occurred. A 12-week in-hospital training program including high-intensity resistance exercises promotes marked strength improvements in patients during the maintenance phase of the treatment for Acute Lymphoblastic Leukemia without side-effects. Parents' evaluations of their children revealed an improvement in the quality of life

  14. Duration of hospitalization as a measure of cost on Children's Cancer Group acute lymphoblastic leukemia studies.

    Science.gov (United States)

    Gaynon, P S; Bostrom, B C; Hutchinson, R J; Lange, B J; Nachman, J B; Steinherz, P G; Sensel, M G; Lee, M K; Stram, D O; Sather, H N

    2001-04-01

    We used duration of hospitalization as a surrogate for cost and event-free survival as a measure of effectiveness to estimate the cost-effectiveness ratios of various treatment regimens on Children's Cancer Group trials for acute lymphoblastic leukemia. The analyses included 4,986 children (2 to 21 years of age) with newly diagnosed acute lymphoblastic leukemia enrolled onto risk-adjusted protocols between 1988 and 1995. Analyses were based on a model of 100 patients. The marginal cost-effectiveness ratio (hospital days per additional patient surviving event-free) was the difference in total duration of hospitalization divided by the difference in number of event-free survivors at 5 years for two regimens. Relapse-adjusted marginal cost of frontline therapy was the difference in total duration of hospitalization for frontline therapy plus relapse therapy divided by the difference in number of event-free survivors at 5 years on the frontline therapy for two regimens. One or two delayed intensification (DI) phases, augmented therapy, and dexamethasone all improved outcome. Marginal cost-effectiveness of these regimens compared with the control regimens was 133 days per patient for DI, 117 days per patient for double DI, and 41 days per patient for augmented therapy. Dexamethasone resulted in 17 fewer days per patient. Relapse-adjusted marginal costs were 68 days per patient for DI and 52 days for double DI. Augmented therapy and dexamethasone-based therapy resulted in 16 and 82 fewer hospital days, respectively. The estimated cost-effectiveness for treating any first relapse was 250 days per patient. DI, double DI, augmented therapy, and dexamethasone-based therapy are cost-effective strategies compared with current treatment of first relapse.

  15. Diagnosis of a case of relapse of acute lymphoblastic leukemia based on oral manifestation of leukemic gingival enlargement and acute necrotizing gingivitis: A case report

    Directory of Open Access Journals (Sweden)

    Gopikrishna Kolli

    2014-01-01

    Full Text Available Acute leukemias are the most common malignancy in childhood. They represent approximately 30% of malignant diseases in patients under the age of 15 years. Acute lymphoblastic leukemia (ALL is the most frequent type of leukemia in children. Despite high cure rates, approximately 20% of patients with ALL have disease relapse. Oral manifestations are common in leukemia, particularly in acute leukemias. One of the oral manifestations of leukemia is diffuse gingival enlargement thought to be, at least partly, the result of gross infiltration of the gingiva by blast cells. The occurrence of acute necrotizing gingivitis, although a rare occurrence, is seen in such immunocompromised individuals. This is a case report of a 19-year-old patient who was under remission after treatment for ALL in whom a recurrence of leukemia was detected based on the oral findings and highlights the importance of its early detection by the dentist in preventing further complications and for instituting therapy swiftly.

  16. Post-induction residual leukemia in childhood acute lymphoblastic leukemia quantified by PCR correlates with in vitro prednisolone resistance

    DEFF Research Database (Denmark)

    Schmiegelow, K; Nyvold, C; Seyfarth, J

    2001-01-01

    Most prognostic factors in childhood acute lymphoblastic leukemia (ALL) are informative for groups of patients, whereas new approaches are needed to predict the efficacy of chemotherapy for the individual patient. The residual leukemia following 4 weeks of induction therapy with prednisolone......, vincristine, doxorubicin and i.t. methotrexate and the in vitro resistance to prednisolone, vincristine, and doxorubicin were measured in 30 boys and 12 girls with B (n = 34) or T lineage (n = 8) ALL. The residual leukemia was quantified after 2 (MRD-D15, n = 29) and 4 weeks (MRD-PI, n = 42) of induction.......05-668). Both MRD-D15 and MRD-PI correlated significantly with the in vitro resistance to prednisolone (MRD-D15: rs = 0.41, P = 0.03; MRD-PI: rs = 0.39, P = 0.01); but not to in vitro vincristine or doxorubicin resistance. The correlations between MRD and in vitro prednisolone resistance were even more...

  17. 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.

  18. 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.

  19. 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.

  20. Ultrasound and MR Findings of Aleukemic Leukemia Cutis in a Patient with Complete Remission of Acute Lymphoblastic Leukemia: A Case Report

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    Kim, Min Sung; Jee, Won Hee; Kim, Sun Ki; Lee, So Yeon; Lim, Gye Yeon; Park, Gyeong Sin; Lee, Seok [Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2010-12-15

    Aleukemic leukemia cutis is an extremely rare condition characterized by the infiltration of leukemic cells in skin without blasts in the peripheral blood. Leukemia cutis is considered a grave prognostic sign, thus early diagnosis is important. Leukemia cutis usually occurs in patients with myeloid leukemia. To the best of our knowledge, there has been no report regarding the radiological findings of aleukemic leukemia cutis, which is probably due to the presence of the skin changes in most patients. We report the ultrasound and MR findings of aleukemic leukemia cutis, even without the skin manifestation in patients with a history of complete remission of the acute lymphoblastic leukemia following an allogeneic peripheral blood stem cell transplantation

  1. Bilateral parotidomegaly as an initial manifestation of acute lymphoblastic leukemia in a child: A case report and review of literature.

    Science.gov (United States)

    Sneha, Latha Magatha; Subbiah, Kaarthikeyani Sankaravadivelu; Scott, Julius Xavier; Rajendiran, Aruna

    2017-01-01

    The more common causes of parotid enlargement in children are infections and inflammatory conditions. Primary neoplasms of the parotid glands are rare in pediatric age group; however, secondary malignancies have been reported in survivors of childhood leukemia. The parotid glands have been the sites of relapses in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia. However, bilateral parotid involvement as an initial presentation of ALL is rarely reported. We present a case of an 8-year-old boy who presented with bilateral parotid enlargement as an initial manifestation of ALL. General physicians should be aware of this extramedullary presentation of acute leukemia when they see a child presenting with organomegaly or abnormal blood counts.

  2. 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.

  3. Obesity as the initial manifestation of central nervous system relapse of acute lymphoblastic leukemia: Case report and literature review

    Directory of Open Access Journals (Sweden)

    Li-Dan Zhang

    2012-01-01

    Full Text Available 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.

  4. Immature MEF2C-dysregulated T-cell leukemia patients have an early T-cell precursor acute lymphoblastic leukemia gene signature and typically have non-rearranged T-cell receptors

    Science.gov (United States)

    Zuurbier, Linda; Gutierrez, Alejandro; Mullighan, Charles G.; Canté-Barrett, Kirsten; Gevaert, A. Olivier; de Rooi, Johan; Li, Yunlei; Smits, Willem K.; Buijs-Gladdines, Jessica G.C.A.M.; Sonneveld, Edwin; Look, A. Thomas; Horstmann, Martin; Pieters, Rob; Meijerink, Jules P.P.

    2014-01-01

    Three distinct immature T-cell acute lymphoblastic leukemia entities have been described including cases that express an early T-cell precursor immunophenotype or expression profile, immature MEF2C-dysregulated T-cell acute lymphoblastic leukemia cluster cases based on gene expression analysis (immature cluster) and cases that retain non-rearranged TRG@ loci. Early T-cell precursor acute lymphoblastic leukemia cases exclusively overlap with immature cluster samples based on the expression of early T-cell precursor acute lymphoblastic leukemia signature genes, indicating that both are featuring a single disease entity. Patients lacking TRG@ rearrangements represent only 40% of immature cluster cases, but no further evidence was found to suggest that cases with absence of bi-allelic TRG@ deletions reflect a distinct and even more immature disease entity. Immature cluster/early T-cell precursor acute lymphoblastic leukemia cases are strongly enriched for genes expressed in hematopoietic stem cells as well as genes expressed in normal early thymocyte progenitor or double negative-2A T-cell subsets. Identification of early T-cell precursor acute lymphoblastic leukemia cases solely by defined immunophenotypic criteria strongly underestimates the number of cases that have a corresponding gene signature. However, early T-cell precursor acute lymphoblastic leukemia samples correlate best with a CD1 negative, CD4 and CD8 double negative immunophenotype with expression of CD34 and/or myeloid markers CD13 or CD33. Unlike various other studies, immature cluster/early T-cell precursor acute lymphoblastic leukemia patients treated on the COALL-97 protocol did not have an overall inferior outcome, and demonstrated equal sensitivity levels to most conventional therapeutic drugs compared to other pediatric T-cell acute lymphoblastic leukemia patients. PMID:23975177

  5. 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

  6. 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

    2017-05-15

    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; 23(10); 2528-41. ©2016 AACR. ©2016 American Association for Cancer Research.

  7. Isocitrate dehydrogenase mutation hot spots in acute lymphoblastic leukemia and oral cancer

    Directory of Open Access Journals (Sweden)

    Jen-Yang Tang

    2012-03-01

    Full Text Available Isocitrate dehydrogenase (IDH encodes a nicotinamide adenine dinucleotide phosphate+-dependent enzyme for oxidative decarboxylation of isocitrate and has an essential role in the tricarboxylic acid cycle. Mutations of IDH1 and IDH2 have been identified in patients with glioma, leukemia, and other cancers. However, the incidence of IDH mutations in acute myeloid leukemia in Taiwan is much lower than that reported in Western countries. The reason for the difference is unknown and its clinical implications remain unclear. Acute lymphoblastic leukemia (ALL is a heterogenous hematopoietic malignancy. Oral squamous cell carcinoma (OSCC results from chronic carcinogen exposures and is highly prevalent in trucking workers, especially in southern Taiwan. Subtypes of both diseases require specific treatments, and molecular markers for developing tailored treatments are limited. High-resolution melting (HRM analysis is now a widely used methodology for rapid, accurate, and low-cost mutation scanning. In this study, 90 adults with OSC and 31 children with ALL were scanned by HRM analysis for IDH1 and IDH2 mutation hot spots. In ALL, the allele frequency was 3.23% in both IDH1 and IDH2. In OSCC, the allele frequency was 2.22% in IDH2. A synonymous mutation over pG313 (c.939A > G of IDH2 was found in both pediatric ALL and adult OSCC. Therefore, we concluded that mutations of IDH are uncommon in ALL and OSCC and are apparently not a major consideration when selecting treatment modalities.

  8. [Bilateral leukemic optic nerve infiltration as the first manifestation of extramedullary relapse in T-cell acute lymphoblastic leukemia].

    Science.gov (United States)

    Amer, Radgonde; David, Ran; Dotan, Shlomo

    2013-02-01

    T-cell acute lymphoblastic leukemia is a hematologic malignancy with propensity to involve extramedullary organs including the eyes. Optic nerve infiltration is relatively rare. This is the case study of a 25-year-old- man who was in full remission following treatment for T-cell acute lymphoblastic leukemia and presented with bilateral leukemic optic nerve infiltration as the first manifestation of extramedullary relapse. The patient was treated with urgent radiotherapy and systemic dexamethasone. Over the following period, gradual resolution of optic disc swelling was noted in both eyes with marked improvement in vision in the right eye. Unfortunately, a few weeks later, a full blown hematological relapse was diagnosed. Salvage chemotherapy was instituted but was complicated by tumor lysis syndrome and septicemia that proved to be fatal. Ophthalmic assessment is essential in patients with hematological malignancies in order to diagnose ocular involvement as a result of malignant infiltration, hematological disturbances or as a complication of systemic therapy.

  9. 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

  10. N-Me, a long range oncogenic enhancer in T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    Herranz, Daniel; Ambesi-Impiombato, Alberto; Palomero, Teresa; Schnell, Stephanie A.; Belver, Laura; Wendorff, Agnieszka A.; Xu, Luyao; Castillo-Martin, Mireia; Llobet-Navás, David; Cardo, Carlos Cordon; Clappier, Emmanuelle; Soulier, Jean; Ferrando, Adolfo A.

    2014-01-01

    Efforts to identify and annotate cancer driver genetic lesions have been almost exclusively focused on the analysis of protein coding genes. Here we identify a new long-range acting MYC enhancer controlled by NOTCH1, targeted by recurrent chromosomal duplications in human T-cell acute lymphoblastic leukemia (T-ALL). This highly conserved regulatory element, hereby named N-Me for NOTCH MYC enhancer, is located within a broad super-enhancer region +1.47 Mb from the MYC transcription initiating site, interacts with the MYC proximal promoter and induces orientation-independent MYC expression in reporter assays. Moreover, analysis of N-Me knockout mice demonstrates a selective and essential role of this regulatory element during thymocyte development and in NOTCH1-induced T-ALL. Altogether, these results identify N-Me as a long range oncogenic enhancer directly implicated in the pathogenesis of human leukemia and highlight the fundamental importance of the NOTCH1-MYC regulatory axis in T-cell transformation and as therapeutic target in T-ALL. PMID:25194570

  11. Genomic and transcriptional landscape of P2RY8-CRLF2-positive childhood acute lymphoblastic leukemia

    Science.gov (United States)

    Vesely, C; Frech, C; Eckert, C; Cario, G; Mecklenbräuker, A; zur Stadt, U; Nebral, K; Kraler, F; Fischer, S; Attarbaschi, A; Schuster, M; Bock, C; Cavé, H; von Stackelberg, A; Schrappe, M; Horstmann, M A; Mann, G; Haas, O A; Panzer-Grümayer, R

    2017-01-01

    Children with P2RY8-CRLF2-positive acute lymphoblastic leukemia have an increased relapse risk. Their mutational and transcriptional landscape, as well as the respective patterns at relapse remain largely elusive. We, therefore, performed an integrated analysis of whole-exome and RNA sequencing in 41 major clone fusion-positive cases including 19 matched diagnosis/relapse pairs. We detected a variety of frequently subclonal and highly instable JAK/STAT but also RTK/Ras pathway-activating mutations in 76% of cases at diagnosis and virtually all relapses. Unlike P2RY8-CRLF2 that was lost in 32% of relapses, all other genomic alterations affecting lymphoid development (58%) and cell cycle (39%) remained stable. Only IKZF1 alterations predominated in relapsing cases (P=0.001) and increased from initially 36 to 58% in matched cases. IKZF1’s critical role is further corroborated by its specific transcriptional signature comprising stem cell features with signs of impaired lymphoid differentiation, enhanced focal adhesion, activated hypoxia pathway, deregulated cell cycle and increased drug resistance. Our findings support the notion that P2RY8-CRLF2 is dispensable for relapse development and instead highlight the prominent rank of IKZF1 for relapse development by mediating self-renewal and homing to the bone marrow niche. Consequently, reverting aberrant IKAROS signaling or its disparate programs emerges as an attractive potential treatment option in these leukemias. PMID:27899802

  12. Mouse xenograft modeling of human adult acute lymphoblastic leukemia provides mechanistic insights into adult LIC biology

    Science.gov (United States)

    Dey, Aditi; Castleton, Anna Z.; Schwab, Claire; Samuel, Edward; Sivakumaran, Janani; Beaton, Brendan; Zareian, Nahid; Zhang, Christie Yu; Rai, Lena; Enver, Tariq; Moorman, Anthony V.; Fielding, Adele K.

    2014-01-01

    The distinct nature of acute lymphoblastic leukemia (ALL) in adults, evidenced by inferior treatment outcome and different genetic landscape, mandates specific studies of disease-initiating mechanisms. In this study, we used NOD/LtSz-scid IL2Rγ nullc (NSG) mouse xenotransplantation approaches to elucidate leukemia-initiating cell (LIC) biology in primary adult precursor B (pre-B) ALL to optimize disease modeling. In contrast with xenografting studies of pediatric ALL, we found that modification of the NSG host environment using preconditioning total body irradiation (TBI) was indispensable for efficient engraftment of adult non-t(4;11) pre-B ALL, whereas t(4;11) pre-B ALL was successfully reconstituted without this adaptation. Furthermore, TBI-based xenotransplantation of non-t(4;11) pre-B ALL enabled detection of a high frequency of LICs (<1:6900) and permitted frank leukemic engraftment from a remission sample containing drug-resistant minimal residual disease. Investigation of TBI-sensitive stromal-derived factor-1/chemokine receptor type 4 signaling revealed greater functional dependence of non-t(4;11) pre-B ALL on this niche-based interaction, providing a possible basis for the differential engraftment behavior. Thus, our studies establish the optimal conditions for experimental modeling of human adult pre-B ALL and demonstrate the critical protumorogenic role of microenvironment-derived SDF-1 in regulating adult pre-B LIC activity that may present a therapeutic opportunity. PMID:24825861

  13. 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

  14. Emerging role of immunotherapy in precursor B-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Valecha, Gautam Kishore; Ibrahim, Uroosa; Ghanem, Sassine; Asti, Divya; Atallah, Jean-Paul; Terjanian, Terenig

    2017-09-01

    Acute lymphoblastic leukemia (ALL) is an aggressive type of leukemia that carries poor prognosis in adults especially in the setting of high risk cytogenetics and relapsed/refractory (R/R) disease. Advancements in immunotherapy have led to the development of several monoclonal antibodies (MoAbs) and chimeric antigen receptor (CAR) T cells that are capable of targeting certain surface antigens on leukemic cells, resulting in their destruction. Areas covered: This article reviews the mechanism of action, outcomes of various trials, and adverse effects of MoAbs and CAR-T cells used in the treatment of precursor B-cell ALL. Expert commentary: Some of the immunotherapeutic agents that have been approved for the treatment of R/R precursor B-cell ALL have shown superior efficacy and safety profile compared to chemotherapy in advanced disease. Several trials are now being conducted to evaluate the role of certain MoAbs in combination with chemotherapy in the treatment of B-cell ALL. Additionally, their use in the frontline setting with more favorable host characteristics may also result in superior outcomes compared to the current standard of care.

  15. Bortezomib combined with standard induction chemotherapy in Japanese children with refractory acute lymphoblastic leukemia.

    Science.gov (United States)

    Iguchi, Akihiro; Cho, Yuko; Sugiyama, Minako; Terashita, Yukayo; Ariga, Tadashi; Hosoya, Yosuke; Hirabayashi, Shinsuke; Manabe, Atsushi; Hara, Keisuke; Aiba, Tetsuya; Shiokawa, Tsugumi; Tada, Hiroko; Sato, Norihiro

    2017-08-01

    Bortezomib has been shown to be effective and well-tolerated in patients with refractory acute lymphoblastic leukemia (ALL) in the Therapeutic Advances in Childhood Leukemia trial. However, the safety and efficacy of bortezomib have not been evaluated in Japanese pediatric patients. Here, we report the results of a clinical trial designed to evaluate the safety of bortezomib combined with induction chemotherapy in Japanese children with refractory ALL. A total of six patients with B-precursor ALL were enrolled in this study. Four-dose bortezomib (1.3 mg/m(2)/dose) combined with two standard induction chemotherapies was used. Prolonged pancytopenia (grade 4) was observed in all patients. Four of the six patients developed severe infectious complications. Peripheral neuropathy (grade 2) occurred in five patients. The individual plasma bortezomib concentration-time profiles were not related to toxicity and efficacy. Five patients were evaluable for response, and four patients achieved complete response (CR) or CR without platelet recovery (80%). In conclusion, four-dose bortezomib (1.3 mg/m(2)/dose) combined with standard re-induction chemotherapy was associated with a high risk of infectious complications induced by prolonged neutropenia, although high efficacy has been achieved for Japanese pediatric patients with refractory ALL. Attention must be given to severe infectious complications when performing re-induction chemotherapy including bortezomib.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. How I treat T-cell acute lymphoblastic leukemia in adults.

    Science.gov (United States)

    Litzow, Mark R; Ferrando, Adolfo A

    2015-08-13

    T-cell immunophenotype of acute lymphoblastic leukemia (T-ALL) is an uncommon aggressive leukemia that can present with leukemic and/or lymphomatous manifestations. Molecular studies are enhancing our understanding of the pathogenesis of T-ALL, and the discovery of activating mutations of NOTCH1 and FBXW7 in a majority of patients has been a seminal observation. The use of pediatric intensive combination chemotherapy regimens in adolescents and young adults has significantly improved the outcome of patients with T-ALL. The use of nelarabine for relapsed and refractory T-ALL results in responses in a substantial minority of patients. Allogeneic hematopoietic cell transplantation (HCT) still plays a key role in patients with high-risk or relapsed/refractory disease. γ-Secretase inhibitors hold promise for the treatment of patients with NOTCH1 mutations, and the results of clinical trials with these agents are eagerly awaited. It is recommended that younger patients receive a pediatric-intensive regimen. Older and unfit patients can receive suitable multiagent chemotherapy and be allocated to HCT based on their response, risk factors, and comorbidities. Although advances in the treatment of T-ALL have lagged behind those of B-cell ALL, it is hoped that the molecular revolution will enhance our understanding of the pathogenesis and treatment of this aggressive lymphoid malignancy. © 2015 by The American Society of Hematology.

  18. Osteonecrosis as a complication in pediatric patients with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Ilaria Riccio

    2016-11-01

    Full Text Available Osteonecrosis is a significant adverse effect of treatment administered to children suffering from acute lymphoblastic leukemia (ALL that may have a negative effect on the quality of life. The purpose of this study is to evaluate the rate of secondary vascular osteonecrosis (ON in a population of pediatric patients with ALL treated with corticosteroids and cytostatic agents. A retrospective analysis of prospectively collected data of the medical records of 328 patients with ALL identified 4 cases with ON, corresponding to 1.2% of all cases observed. Of the 4 patients identified in our study 3 were girls and 1 was a boy, aged from 10 to 16 years old (average age at diagnosis, 12 years. Median time between the diagnosis of ALL and ON was 12.5 months (range, 12 to 36 months. Regarding the lesion size of ON, in all cases the femoral head (monolateral in 1 case and bilateral in 3 cases was involved and was associated with the scapula-humeral joint in one case. ON of the weight-bearing joints has been identified as a severe complication in children with leukemia that may be associated with the development of articular surface collapse, subsequent debilitating arthritis, sometimes needing arthroplasty. For this reason it is very important to implement prevention strategies, especially in adolescent girls treated with steroids and chemotherapy. An early diagnosis of ON and careful orthopedic follow-up are necessary in order to avoid bone deformations related to the late start or the wrong therapy.

  19. Osteonecrosis as a complication in pediatric patients with acute lymphoblastic leukemia.

    Science.gov (United States)

    Riccio, Ilaria; Pota, Elvira; Marcarelli, Marco; Affinita, Maria Carmen; Di Pinto, Daniela; Indolfi, Cristiana; Del Regno, Nicola; Esposito, Marco

    2016-11-28

    Osteonecrosis is a significant adverse effect of treatment administered to children suffering from acute lymphoblastic leukemia (ALL) that may have a negative effect on the quality of life. The purpose of this study is to evaluate the rate of secondary vascular osteonecrosis (ON) in a population of pediatric patients with ALL treated with corticosteroids and cytostatic agents. A retrospective analysis of prospectively collected data of the medical records of 328 patients with ALL identified 4 cases with ON, corresponding to 1.2% of all cases observed. Of the 4 patients identified in our study 3 were girls and 1 was a boy, aged from 10 to 16 years old (average age at diagnosis, 12 years). Median time between the diagnosis of ALL and ON was 12.5 months (range, 12 to 36 months). Regarding the lesion size of ON, in all cases the femoral head (monolateral in 1 case and bilateral in 3 cases) was involved and was associated with the scapula-humeral joint in one case. ON of the weight-bearing joints has been identified as a severe complication in children with leukemia that may be associated with the development of articular surface collapse, subsequent debilitating arthritis, sometimes needing arthroplasty. For this reason it is very important to implement prevention strategies, especially in adolescent girls treated with steroids and chemotherapy. An early diagnosis of ON and careful orthopedic follow-up are necessary in order to avoid bone deformations related to the late start or the wrong therapy.

  20. Oral manifestations in pediatric patients receiving chemotherapy for acute lymphoblastic leukemia.

    Science.gov (United States)

    Ponce-Torres, Elena; Ruíz-Rodríguez, Ma del Socorro; Alejo-González, Francisco; Hernández-Sierra, Juan Francisco; Pozos-Guillén, Amaury de J

    2010-01-01

    The purpose of this study was to determine the prevalence of oral manifestations in pediatric patients with acute lymphoblastic leukemia (ALL) receiving chemotherapy, and to evaluate the significance of independent risk factors (oral health, gender, age, time and type of treatment, and phase of chemotherapy). A cross-sectional study was made in 49 children with ALL between 2 and 14 years of age. To describe oral manifestations, a clinical diagnosis was made and the following criteria were applied: the OHI-S index to describe oral health and the IMPA index to describe periodontal conditions and to differentiate gingivitis from periodontitis. The prevalence of oral manifestations was: gingivitis, 91.84%; caries, 81.63%; mucositis, 38.77%; periodontitis, 16.32%; cheilitis, 18.36%; recurrent herpes, 12.24%; and primary herpetic gingivostomatitis, 2.04%. Other oral manifestations were: dry lips, mucosal pallor, mucosal petechiae, ecchymoses, and induced ulcers. The prevalence of oral candidiasis was 6.12%. It was observed that high risk ALL and poor oral hygiene were important risk factors for the development of candidiasis and gingivitis. The type of leukemia, gender and phase of chemotherapy were apparently associated with the presence of candidiasis, gingivitis, and periodontitis, and they could be considered risk factors for the development of oral manifestations.

  1. The role of adipose tissue and obesity in causing treatment resistance of acute lymphoblastic leukemia.

    Science.gov (United States)

    Sheng, Xia; Mittelman, Steven D

    2014-01-01

    Obesity is responsible for ~90,000 cancer deaths/year, increasing cancer incidence and impairing its treatment. Obesity has also been shown to impact hematological malignancies, through as yet unknown mechanisms. Adipocytes are present in bone marrow and the microenvironments of many types of cancer, and have been found to promote cancer cell survival. In this review, we explore several ways in which obesity might cause leukemia treatment resistance. Obese patients may be at a treatment disadvantage due to altered pharmacokinetics of chemotherapy and dosage "capping" based on ideal body weight. The adipose tissue provides fuel to cancer cells in the form of amino acids and free fatty acids. Adipocytes have been shown to cause cancer cells to resist chemotherapy-induced apoptosis. In addition, obese adipose tissue is phenotypically altered, producing a milieu of pro-inflammatory adipokines and cytokines, some of which have been linked to cancer progression. Given the prevalence of obesity, understanding its role and adipose tissue in acute lymphoblastic leukemia treatment is necessary for evaluating current treatment regimen and revealing new therapeutic targets.

  2. 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

    2013-11-01

    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.

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

    OpenAIRE

    Aberuyi, N; S. Rahgozar; 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. ASSESSMENT OF OBESITY AND HEPATIC LATE ADVERSE EFFECTS IN THE EGYPTIAN SURVIVORS OF PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA: SINGLE CENTER STUDY

    OpenAIRE

    Farida El-Rashedy; Mahmoud Ahmed El-Hawy; Sally El Hefnawy; Mona Mohammed

    2017-01-01

    BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) with current cure rates reaching 80% emphasizes the necessity to determine treatment related long-term effects. The aim of this study is to estimate the prevalence of overweight, obesity and hepatic late adverse effects in a cohort of ALL survivors treated at the Hematology and Oncology Unit, Pediatrics Department, Menoufia University, Egypt. METHODS: In this case control study, height, weight and body mass index (BMI) were assessed...

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

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    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.

  6. Predicting trajectories of behavioral adjustment in children diagnosed with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Nicolaas, S.M. Sint; Hoogerbrugge, P.M.; Bergh, E.M. van den; Custers, J.A.E.; Gameiro, S.; Gemke, R.J.; Verhaak, C.M.

    2016-01-01

    PURPOSE: Previous research showed that children with cancer are at risk for developing behavioral adjustment problems after successful treatment; however, the course of adjustment remains unclear. This study focuses on adjustment trajectories of children during treatment for acute lymphoblastic

  7. 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 lymphoblast...

  8. High lifetime incidence of adult acute lymphoblastic leukemia among Hispanics in California.

    Science.gov (United States)

    Pullarkat, Sheeja T; Danley, Kathleen; Bernstein, Leslie; Brynes, Russell K; Cozen, Wendy

    2009-02-01

    The higher incidence of acute lymphoblastic leukemia (ALL) among Hispanic children relative to that in other racial/ethnic groups is well-known. We evaluated the incidence patterns of ALL in adults. We analyzed the incidence patterns of ALL (International Classification of Diseases for Oncology 3 codes 9835-9837) among all patients diagnosed from 1988 to 2004 in California using data from the California Cancer Registry to determine whether adult Hispanics also had higher incidence rates of ALL compared with non-Hispanic Whites (Whites). Age-adjusted incidence rates (AAIR), incidence rate ratios (IRR), and 5-year survival rates were obtained using SEER*Stat. AAIRs of other leukemia subtypes and IRRs relative to non-Hispanic Whites were also examined as references for ALL. AAIRs of ALL in Hispanic males and females ages 20 to 54 years were higher compared with those in White males and females (IRR, 1.99; 95% confidence interval, 1.74-2.28 and IRR, 1.91; 95% confidence interval, 1.60-2.25, respectively). A higher AAIR of ALL was also observed among older (55+ years) Hispanic females (IRR, 1.84; 95% confidence interval, 1.52-2.21), but not in males (IRR, 1.07; 95% confidence interval, 0.84-1.34). Among Hispanics, low socioeconomic status was associated with a higher AAIR compared with high/middle socioeconomic status (IRR, 1.33; 95% confidence interval, 1.04-1.70). The respective 5-year survival rates among ALL patients were 38% and 30% for Whites and Hispanics ages 20 to 54 years, and 8% and 12% for patients 55 years of age or older. Compared with other racial/ethnic groups, Hispanics did not have an increased IRR of the other major leukemia subtypes. Hispanics experience a higher incidence of ALL throughout life, but not other subtypes.

  9. 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.

  10. Proposal for the standardization of flow cytometry protocols to detect minimal residual disease in acute lymphoblastic leukemia

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    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.

  11. Proposal for the standardization of flow cytometry protocols to detect minimal residual disease in acute lymphoblastic leukemia

    Science.gov (United States)

    Ikoma, Maura Rosane Valério; Beltrame, Miriam Perlingeiro; Ferreira, Silvia Inês Alejandra Cordoba Pires; Souto, Elizabeth Xisto; Malvezzi, Mariester; Yamamoto, Mihoko

    2015-01-01

    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. PMID:26670404

  12. 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.

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

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    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.

  14. Triple intrathecal therapy alone with omission of cranial radiation in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Liu, Hsi-Che; Yeh, Ting-Chi; Hou, Jen-Yin; Chen, Kuan-Hao; Huang, Ting-Huan; Chang, Ching-Yi; Liang, Der-Cherng

    2014-06-10

    To eliminate the toxicities and sequelae of cranial irradiation (CrRT) and to minimize the adverse impact of traumatic lumbar puncture (TLP) with blasts, a prospective study of a modified CNS-directed therapy was conducted in children with acute lymphoblastic leukemia (ALL). Since June 1999, children with newly diagnosed ALL have been treated with triple intrathecal therapy (TIT) alone without CrRT. The first TIT was delayed until the disappearance of blasts from peripheral blood (PB) for up to 10 days of multidrug induction, and CrRT was omitted in all patients. If PB blasts persisted on treatment day 10 (d10), the TIT was then performed. Of a total of 156 patients, 152 were eligible. Seventeen patients did not have PB blasts at diagnosis. Three fourths of the remaining patients achieved complete clearance of PB blasts by d10. Only hyperleukocytosis at diagnosis showed a significantly lower clearance rate. Six standard-risk patients were upgraded to high risk because of detectable PB blasts on d10. TLPs were encountered in four patients (2.6%), but none were contaminated with lymphoblasts. Neither CNS-2 (less than 5 WBCs/μL with blasts in a nontraumatic sample) nor CNS-3 (≥5 WBCs/μL with blasts in a nontraumatic sample or the presence of cranial nerve palsy) was present. The 5-year event-free survival and overall survival rates±SE were 84.2%±3.0% and 90.6%±2.4%, respectively. No isolated CNS relapse occurred, but two patients experienced combined CNS relapses. The 7-year cumulative risk of any CNS relapse was 1.4%±1.0%. Delaying first TIT until circulating blasts have cleared may improve CNS control in children with newly diagnosed ALL and preclude the need for CrRT. © 2014 by American Society of Clinical Oncology.

  15. MicroRNA-101 regulates T-cell acute lymphoblastic leukemia progression and chemotherapeutic sensitivity by targeting Notch1.

    Science.gov (United States)

    Qian, Lu; Zhang, Wanggang; Lei, Bo; He, Aili; Ye, Lianhong; Li, Xingzhou; Dong, Xin

    2016-11-01

    The present study aimed to investigate the role of microRNA (miR)-101 in acute lymphoblastic leukemia progression and chemoresistance. Furthermore, a novel target gene of miR-101 was identified. Here, we confirmed that miR-101 was significantly downregulated in the blood samples of patients with T-cell acute lymphoblastic leukemia (T-ALL) compared with the healthy controls, as determined by reverse transcription quantitative polymerase chain reaction (RTqPCR) analysis. The in vitro experiments demonstrated that miR-101 significantly repressed the proliferation and invasion, and induced potent apoptosis in Jurkat cells, as determined by CCK-8, flow cytometer and cell invasion assays. Luciferase assay confirmed that Notch1 was a target gene of miR-101, and western blotting showed that miR-101 suppressed the expression of Notch1 at the protein level. Moreover, functional restoration assays revealed that Notch1 mediates the effects of miR-101 on Jurkat cell proliferation, apoptosis and invasion. miR-101 enhanced the sensitivity of Jurkat cells to the chemotherapeutic agent adriamycin. Taken together, our results show for the first time that miR-101 acts as a tumor suppressor in T-cell acute lymphoblastic leukaemia and it could enhance chemotherapeutic sensitivity. Furthermore, Notch1 was identified to be a novel target of miR-101. This study indicates that miR-101 may represent a potential therapeutic target for T-cell acute lymphoblastic leukemia intervention.

  16. MINIMAL REQUIREMENTS FOR THE DIAGNOSIS, CLASSIFICATION, AND EVALUATION OF THE TREATMENT OF CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA (ALL) IN THE BFM FAMILY COOPERATIVE GROUP

    NARCIS (Netherlands)

    VANDERDOESVANDENBERG, A; BARTRAM, CR; BASSO, G; BENOIT, YCM; BIONDI, A; DEBATIN, KM; HAAS, OA; HARBOTT, J; KAMPS, WA; KOLLER, U; LAMPERT, F; LUDWIG, WD; NIEMEYER, CM; VANWERING, ER

    1992-01-01

    Minimal requirements and their rationale for the diagnosis and the response to treatment in childhood acute lymphoblastic leukemia (ALL) were defined in the recently instituted "BFM-Family"-Group, in which the German, Austrian, Dutch, Italian, Belgian, French and Hungarian childhood leukemia study

  17. Acute Leukemia in Children

    Directory of Open Access Journals (Sweden)

    K.V. Vilchevska

    2014-11-01

    Full Text Available The lecture presents current data on the etiology, pathogenesis, clinical manifestations, observation methods and principles of treatment of children with acute lymphoblastic leukemia. own clinical observation of development of the acute lymphoblastic leukemia clinical picture in a child aged 4 years old has been described. This case is characterized by late diagnosis and inappropriate prescription of steroids in combination with antipyretic agents that led to tumor resistance to the treatment.

  18. MicroRNA-205 downregulates mixed-lineage-AF4 oncogene expression in acute lymphoblastic leukemia

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    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

  19. Identification of fusion genes and characterization of transcriptome features in T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Chen, Bing; Jiang, Lu; Zhong, Meng-Ling; Li, Jian-Feng; Li, Ben-Shang; Peng, Li-Jun; Dai, Yu-Ting; Cui, Bo-Wen; Yan, Tian-Qi; Zhang, Wei-Na; Weng, Xiang-Qin; Xie, Yin-Yin; Lu, Jing; Ren, Rui-Bao; Chen, Su-Ning; Hu, Jian-Da; Wu, De-Pei; Chen, Zhu; Tang, Jing-Yan; Huang, Jin-Yan; Mi, Jian-Qing; Chen, Sai-Juan

    2018-01-09

    T-cell acute lymphoblastic leukemia (T-ALL) is a clonal malignancy of immature T cells. Recently, the next-generation sequencing approach has allowed systematic identification of molecular features in pediatric T-ALL. Here, by performing RNA-sequencing and other genomewide analysis, we investigated the genomic landscape in 61 adult and 69 pediatric T-ALL cases. Thirty-six distinct gene fusion transcripts were identified, with SET-NUP214 being highly related to adult cases. Among 18 previously unknown fusions, ZBTB16-ABL1, TRA-SALL2, and involvement of NKX2-1 were recurrent events. ZBTB16-ABL1 functioned as a leukemogenic driver and responded to the effect of tyrosine kinase inhibitors. Among 48 genes with mutation rates >3%, 6 were newly found in T-ALL. An aberrantly overexpressed short mRNA transcript of the SLC17A9 gene was revealed in most cases with overexpressed TAL1, which predicted a poor prognosis in the adult group. Up-regulation of HOXA, MEF2C, and LYL1 was often present in adult cases, while TAL1 overexpression was detected mainly in the pediatric group. Although most gene fusions were mutually exclusive, they coexisted with gene mutations. These genetic abnormalities were correlated with deregulated gene expression markers in three subgroups. This study may further enrich the current knowledge of T-ALL molecular pathogenesis.

  20. Evaluation of an oral preventive protocol in children with acute lymphoblastic leukemia

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    Costa Edja Maria Melo de Brito

    2003-01-01

    Full Text Available This study was designed to assess the effectiveness of a preventive oral protocol in children receiving antineoplastic treatment for acute lymphoblastic leukemia (ALL before initiating a larger intervention study. During a seven month period, fourteen children from two to ten years old with a diagnosis of ALL were evaluated. Patients with ALL who received a 0.12% chlorhexidine mouth rinse (seven children were compared to a control group of patients who were not given the same preventive treatment (seven children as to the occurrence of oral mucosal complications. Children in both groups received daily oral hygiene care, and were examined daily by the pediatric dentistry team until discharge. A significant decrease in the incidence of oral mucositis and ulceration was observed in the children who received a 0.12% chlorhexidine mouth rinse (p < 0.05 by Fisher's exact test. The findings obtained in the present trial are encouraging, and suggest that the systematic application of a preventive protocol reduces the incidence of oral complications in children with ALL receiving chemotherapy.

  1. Acute lymphoblastic leukemia in adolescents and young adults – from genomics to the clinics

    Directory of Open Access Journals (Sweden)

    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

  2. Updates in the biology and therapy for infant acute lymphoblastic leukemia.

    Science.gov (United States)

    Guest, Erin M; Stam, Ronald W

    2017-02-01

    The prognosis for infants less than 12 months of age who are diagnosed with acute lymphoblastic leukemia (ALL) remains poor despite overall advances in the treatment of childhood ALL. In this review, we highlight the recent advances in the understanding of the pathogenesis of infant ALL and discuss opportunities for translating these findings into clinical trials. Infant ALL can be divided into two major disease types, defined by the presence or absence of KMT2A (MLL) rearrangement (KMT2A-R). Recent molecular profiling studies have found that infant ALL with KMT2A-R is an epigenomic disease that lacks other somatic driver mutations. Strategies to intensify therapy have not improved survival for infants with KMT2A-R ALL. In contrast, infant ALL without KMT2A-R is more similar to ALL of older children and survival has improved modestly with intensification of chemotherapy. Discovery of clonal molecular markers that predict chemoresistance will allow further risk classification and development of novel treatment strategies. Modern clinical trials are integrating molecularly targeted therapies into the treatment of infant ALL. Advances in molecular profiling and integration of targeted therapy have the potential to reduce toxicity and improve survival for infants with ALL.

  3. Feasibility and initial effectiveness of home exercise during maintenance therapy for childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Esbenshade, Adam J; Friedman, Debra L; Smith, Webb A; Jeha, Sima; Pui, Ching-Hon; Robison, Leslie L; Ness, Kirsten K

    2014-01-01

    Children with acute lymphoblastic leukemia (ALL) are at increased risk of obesity and deconditioning from cancer therapy. This pilot study assessed feasibility/initial efficacy of an exercise intervention for patients with ALL undergoing maintenance therapy. Participants were aged 5 to 10 years, receiving maintenance therapy, in first remission. A 6-month home-based intervention, with written and video instruction, was supervised with weekly calls from an exercise coach. Pre- and poststudy testing addressed strength, flexibility, fitness, and motor function. Seventeen patients enrolled (participation 63%). Twelve (71%) finished the intervention, completing 81.7 ± 7.2% of prescribed sessions. Improvements of 5% or more occurred in 67% for knee and 75% for grip strength, 58% for hamstring/low-back and 83% for ankle flexibility, 75% for the 6-Minute Walk Test, and 33% for performance on the Bruininks-Oseretsky Test of Motor Proficiency Version 2. This pilot study demonstrated that exercise intervention during ALL therapy is feasible and has promise for efficacy.

  4. 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.

  5. Monoclonal antibodies and immune therapies for adult precursor B-acute lymphoblastic leukemia.

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    Sikaria, Swati; Aldoss, Ibrahim; Akhtari, Mojtaba

    2016-04-01

    Adult B-acute lymphoblastic leukemia (B-ALL) does not share the favorable prognosis seen in pediatric patients with the same disease. Less than 50% of patients experience long-term survival and for those adults over age 60, long-term survival is only 10%. At time of relapse, 5-year prognosis is a dismal 7%. Novel and less toxic agents are urgently needed. The last few years have seen a surge in immune therapies for B-ALL. These agents may target CD19, CD20, CD22, and less frequently CD52. Expression of these surface markers and the drugs which target them are discussed. Some immune therapies are simple monoclonal antibodies against B lymphocyte markers such as rituximab, ofatumumab, and epratuzumab. Others are in a class of antibody-drug conjugates which link a highly toxic chemotherapy to a monoclonal antibody for targeted delivery, such as inotuzumab and denintuzumab. Finally, novel immune therapies recruit (in the case of bispecific T cell engager [BiTE]) or modify (in the case of chimeric antigen receptor [CAR] T cells) one's own T cells to fight leukemic cells. This article reviews the rationale, clinical data, and toxicity profiles of immune therapies approved or in late stages of development for B-ALL. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  6. The relationship between iron bone marrow stores and response to treatment in pediatric acute lymphoblastic leukemia

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    Moafi, Alireza; Ziaie, Mozhdeh; Abedi, Marjan; Rahgozar, Soheila; Reisi, Nahid; Nematollahi, Pardis; Moafi, Hadi

    2017-01-01

    Abstract Iron is an intracellular element whose accumulation in the body is associated with tissue damage. This study examines the effect of iron on pediatric acute lymphoblastic leukemia (ALL) and its “response to treatment.” At the end of the first year of treatment, bone marrow iron store (BMIS) was evaluated in children with ALL and the relationship between iron store and minimal residual disease was investigated. Moreover, the 3-year disease-free survival (3-DFS) of patients was determined. Patients’ BMIS were compared with that of subjects with normal bone marrow. The study examined 93 children, including 78 Pre-B and 15 T-cell ALL patients. BMIS did not differ between the children with ALL and those with no evidence of cancer. BMIS was increased in 26.6% of patients at the end of the first year of treatment. Drug resistance and BM relapses were more prevalent in cases with high BMIS in both Pre-B and T-cell groups. Bone marrow iron store is not considered a risk factor for childhood ALL. However, high levels of BMIS are associated with poor response to treatment and the risk of relapse. Bone marrow iron store control during treatment can therefore help achieve better outcomes and improve the chances of recovery. PMID:29095311

  7. 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.

  8. Quantitative MRI assessments of white matter in children treated for acute lymphoblastic leukemia

    Science.gov (United States)

    Reddick, Wilburn E.; Glass, John O.; Helton, Kathleen J.; Li, Chin-Shang; Pui, Ching-Hon

    2005-04-01

    The purpose of this study was to use objective quantitative MR imaging methods to prospectively assess changes in the physiological structure of white matter during the temporal evolution of leukoencephalopathy (LE) in children treated for acute lymphoblastic leukemia. The longitudinal incidence, extent (proportion of white matter affect), and intensity (elevation of T1 and T2 relaxation rates) of LE was evaluated for 44 children. A combined imaging set consisting of T1, T2, PD, and FLAIR MR images and white matter, gray matter and CSF a priori maps from a spatially normalized atlas were analyzed with a neural network segmentation based on a Kohonen Self-Organizing Map (SOM). Quantitative T1 and T2 relaxation maps were generated using a nonlinear parametric optimization procedure to fit the corresponding multi-exponential models. A Cox proportional regression was performed to estimate the effect of intravenous methotrexate (IV-MTX) exposure on the development of LE followed by a generalized linear model to predict the probability of LE in new patients. Additional T-tests of independent samples were performed to assess differences in quantitative measures of extent and intensity at four different points in therapy. Higher doses and more courses of IV-MTX placed patients at a higher risk of developing LE and were associated with more intense changes affecting more of the white matter volume; many of the changes resolved after completion of therapy. The impact of these changes on neurocognitive functioning and quality of life in survivors remains to be determined.

  9. 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.

  10. 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.

  11. JAK2 aberrations in childhood B-cell precursor acute lymphoblastic leukemia

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    de Goffau-Nobel, Willemieke; Hoogkamer, Alex Q.; Boer, Judith M.; Boeree, Aurélie; van de Ven, Cesca; Koudijs, Marco J.; Besselink, Nicolle J.M.; de Groot-Kruseman, Hester A.; Zwaan, Christian Michel; Horstmann, Martin A.; Pieters, Rob; den Boer, Monique L.

    2017-01-01

    JAK2 abnormalities may serve as target for precision medicines in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In the current study we performed a screening for JAK2 mutations and translocations, analyzed the clinical outcome and studied the efficacy of two JAK inhibitors in primary BCP-ALL cells. Importantly, we identify a number of limitations of JAK inhibitor therapy. JAK2 mutations mainly occurred in the poor prognostic subtypes BCR-ABL1-like and non- BCR-ABL1-like B-other (negative for sentinel cytogenetic lesions). JAK2 translocations were restricted to BCR-ABL1-like cases. Momelotinib and ruxolitinib were cytotoxic in both JAK2 translocated and JAK2 mutated cells, although efficacy in JAK2 mutated cells highly depended on cytokine receptor activation by TSLP. However, our data also suggest that the effect of JAK inhibition may be compromised by mutations in alternative survival pathways and microenvironment-induced resistance. Furthermore, inhibitors induced accumulation of phosphorylated JAK2Y1007, which resulted in a profound re-activation of JAK2 signaling upon release of the inhibitors. This preclinical evidence implies that further optimization and evaluation of JAK inhibitor treatment is necessary prior to its clinical integration in pediatric BCP-ALL. PMID:29163799

  12. New and emerging prognostic and predictive genetic biomarkers in B-cell precursor acute lymphoblastic leukemia

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    Moorman, Anthony V.

    2016-01-01

    Acute lymphoblastic leukemia (ALL) is a heterogeneous disease at the genetic level. Chromosomal abnormalities are used as diagnostic, prognostic and predictive biomarkers to provide subtype, outcome and drug response information. t(12;21)/ETV6-RUNX1 and high hyper-diploidy are good-risk prognostic biomarkers whereas KMT2A (MLL) translocations, t(17;19)/TCF3-HLF, haploidy or low hypodiploidy are high-risk biomarkers. t(9;22)/BCR-ABL1 patients require targeted treatment (imatinib/dasatinib), whereas iAMP21 patients achieve better outcomes when treated intensively. High-risk genetic biomarkers are four times more prevalent in adults compared to children. The application of genomic technologies to cases without an established abnormality (B-other) reveals copy number alterations which can be used either individually or in combination as prognostic biomarkers. Transcriptome sequencing studies have identified a network of fusion genes involving kinase genes - ABL1, ABL2, PDGFRB, CSF1R, CRLF2, JAK2 and EPOR. In vitro and in vivo studies along with emerging clinical observations indicate that patients with a kinase-activating aberration may respond to treatment with small molecular inhibitors like imatinib/dasatinib and ruxolitinib. Further work is required to determine the true frequency of these abnormalities across the age spectrum and the optimal way to incorporate such inhibitors into protocols. In conclusion, genetic biomarkers are playing an increasingly important role in the management of patients with ALL. PMID:27033238

  13. MTHFR polymorphisms in childhood acute lymphoblastic leukemia: influence on methotrexate therapy

    Directory of Open Access Journals (Sweden)

    Umerez M

    2017-03-01

    Full Text Available Maitane Umerez,1 Ángela Gutierrez-Camino,1 Carmen Muñoz-Maldonado,1 Idoia Martin-Guerrero,1 Africa Garcia-Orad1,2 1Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursery, University of the Basque Country, UPV/EHU, Leioa, 2BioCruces Health Research Institute, Barakaldo, Spain Abstract: Methotrexate (MTX is an important component in the therapy used to treat childhood acute lymphoblastic leukemia (ALL. Methylenetetrahydrofolate reductase (MTHFR is a key enzyme for MTX pharmacokinetics. Two single-nucleotide polymorphisms in MTHFR gene, C677T and A1298C, affecting MTHFR activity, have been widely studied as potential markers of MTX toxicity and/or outcome in pediatric ALL. In this review, we show that the majority of published reports do not find association or present opposite effect. Therefore, MTHFR C677T and A1298C polymorphisms do not seem to be good markers of MTX-related toxicity and/or outcome in pediatric ALL. The efforts should be focused on other genes, such as transporter genes or microRNA-related genes. Keywords: MTHFR, methotrexate, toxicity, outcome, C677T, A1298C

  14. Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles.

    Science.gov (United States)

    Marincevic-Zuniga, Yanara; Dahlberg, Johan; Nilsson, Sara; Raine, Amanda; Nystedt, Sara; Lindqvist, Carl Mårten; Berglund, Eva C; Abrahamsson, Jonas; Cavelier, Lucia; Forestier, Erik; Heyman, Mats; Lönnerholm, Gudmar; Nordlund, Jessica; Syvänen, Ann-Christine

    2017-08-14

    Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL). In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts. We combined fusion gene detection with genome-wide DNA methylation analysis, gene expression profiling, and targeted sequencing to determine molecular signatures of emerging ALL subtypes. We identified 64 unique fusion events distributed among 80 individual patients, of which over 50% have not previously been reported in ALL. Although the majority of the fusion genes were found only in a single patient, we identified several recurrent fusion gene families defined by promiscuous fusion gene partners, such as ETV6, RUNX1, PAX5, and ZNF384, or recurrent fusion genes, such as DUX4-IGH. Our data show that patients harboring these fusion genes displayed characteristic genome-wide DNA methylation and gene expression signatures in addition to distinct patterns in single nucleotide variants and recurrent copy number alterations. Our study delineates the fusion gene landscape in pediatric ALL, including both known and novel fusion genes, and highlights fusion gene families with shared molecular etiologies, which may provide additional information for prognosis and therapeutic options in the future.

  15. Association of the methylenetetrahydrofolate reductase polymorphism in Korean patients with childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Kim, Nam Keun; Chong, So Young; Jang, Moon Ju; Hong, Seung Ho; Kim, Heung Sik; Cho, Eun Kyung; Lee, Jung Ae; Ahn, Myung Ju; Kim, Chul Soo; Oh, Doyeun

    2006-01-01

    Methylenetetrahydrofolate reductase plays a central role in converting folate to methyl donor for DNA methylation. Recently, methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) mutations were discovered to be associated with childhood acute lymphoblastic leukemia (ALL), as well as colon cancer, lymphoma, esophageal and stomach cancer. Therefore, it was hypothesized that the MTHFR polymorphisms are associated with the risk of childhood ALL in the Korean population. DNA samples taken from 66 patients with ALL and 100 age-matched controls were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay for detection of MTHFR C677T and A1298C mutations. The frequency of the AC genotype for MTHFR A1298C polymorphism was significantly different between the controls and the cases (OR, 2.22; CI, 95% 1.09-4.51, p=0.03). The 1298AC+CC genotype was also significantly different (OR, 2.11; 95% CI, 1.06-4.22; p=0.049). There was, however, no significant difference for MTHFR C677T polymorphism and combined genotype frequencies between the two groups. Although no consistent results on associations between MTHFR A 1298C polymorphism and ALL in the populations studied were obtained, the A1298C polymorphism, at least in Koreans, may be a genetic determinant among childhood ALL patients.

  16. Education given to parents of children newly diagnosed with acute lymphoblastic leukemia: the parent's perspective.

    Science.gov (United States)

    Aburn, Gemma; Gott, Meryn

    2014-01-01

    Over the last 30 years, diagnosis and treatment of childhood cancers have improved significantly due to medical research and advancements in technology. Increasingly, parents are taking on the role of providing "nursing" care for their children, including managing emergency situations as well as everyday treatment needs. This study investigated the perceptions and experiences of parents caring for newly diagnosed children with acute lymphoblastic leukemia (ALL) in relation to education given prior to the first discharge from hospital. Using a grounded theory approach, 12 parents of children with ALL from a tertiary pediatric hematology and oncology setting in New Zealand were interviewed using a semi-structured interview technique. Key findings of relevance to clinical practice include the importance of recognizing the emotional strain parents experience following diagnosis and the resultant impact upon how education is understood. Findings may also be applicable to other complex child health areas where education is provided, both in a local and international context. Understanding the family perspective is crucial to enabling clinicians to provide appropriate and informative education to children with ALL and their families.

  17. Oxidative Stress, Motor Abilities, and Behavioral Adjustment in Children Treated for Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Hockenberry, Marilyn J; Krull, Kevin R; Insel, Kathleen C; Harris, Lynnette L; Gundy, Patricia M; Adkins, Kristin B; Pasvogel, Alice E; Taylor, Olga A; Koerner, Kari M; Montgomery, David W; Ross, Adam K; Hill, Adam; Moore, Ida M

    2015-09-01

    To examine associations among oxidative stress, fine and visual-motor abilities, and behavioral adjustment in children receiving chemotherapy for acute lymphoblastic leukemia (ALL)
. A prospective, repeated-measures design
. Two pediatric oncology settings in the southwestern United States. 89 children with ALL were followed from diagnosis to the end of chemotherapy. Serial cerebrospinal fluid samples were collected during scheduled lumbar punctures and analyzed for oxidative stress biomarkers. Children completed fine motor dexterity, visual processing speed, and visual-motor integration measures at three time points. Parents completed child behavior ratings at the same times. Oxidative stress, fine motor dexterity, visual processing, visual-motor integration, and behavioral adjustment
. Children with ALL had below-average fine motor dexterity, visual processing speed, and visual-motor integration following the induction phase of ALL therapy. By end of therapy, visual processing speed normalized, and fine motor dexterity and visual-motor integration remained below average. Oxidative stress measures correlated with fine motor dexterity and visual-motor integration. Decreased motor functioning was associated with increased hyperactivity and anxiety
. Oxidative stress occurs following chemo-therapy for childhood ALL and is related to impaired fine motor skills and visual symptoms
. Early intervention should be considered to prevent fine motor and visual-spatial deficits, as well as behavioral problems.

  18. Minimal residual disease detection in Tunisian B-acute lymphoblastic leukemia based on immunoglobulin gene rearrangements

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    S. Besbes

    Full Text Available IGH gene rearrangement and IGK-Kde gene deletion can be used as molecular markers for the assessment of B lineage acute lymphoblastic leukemia (B-ALL. Minimal residual disease detected based on those markers is currently the most reliable prognosis factor in B-ALL. The aim of this study was to use clonal IGH/IGK-Kde gene rearrangements to confirm B-ALL diagnosis and to evaluate the treatment outcome of Tunisian leukemic patients by monitoring the minimal residual disease (MRD after induction chemotherapy. Seventeen consecutive newly diagnosed B-ALL patients were investigated by multiplex PCR assay and real time quantitative PCR according to BIOMED 2 conditions. The vast majority of clonal VH-JH rearrangements included VH3 gene. For IGK deletion, clonal VK1f/6-Kde recombinations were mainly identified. These rearrangements were quantified to follow-up seven B-ALL after induction using patient-specific ASO. Four patients had an undetectable level of MRD with a sensitivity of up to 10-5. This molecular approach allowed identification of prognosis risk group and adequate therapeutic decision. The IGK-Kde and IGH gene rearrangements might be used for diagnosis and MRD monitoring of B-ALL, introduced for the first time in Tunisian laboratories.

  19. Effect of Malnutrition at Diagnosis on Clinical Outcomes of Children With Acute Lymphoblastic Leukemia.

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    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 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.

  20. Evaluation of Structural Factors Potentially Implicated in Acute Lymphoblastic Leukemia: A report of the MIGICCL.

    Science.gov (United States)

    López-Sánchez, Dulce María; Méndez-Tenorio, Alfonso; Roacho-Pérez, Jorge Alberto; Rangel-López, Angélica

    2016-10-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer in the pediatric population; ∼80% of the cases show some translocation. Translocations that result in ALL are due to chromosome breaks. However, the exact mechanisms that cause these breaks have not been well studied. A detailed search of the breakpoints associated with ALL reported in the NCBI database shows that some are concentrated in limited regions of the chromosome, whereas others are scattered throughout. Therefore, the objective of this study was to identify the structural factors involved in chromosomal breaks in ALL. We performed several bioinformatic studies on the sequences where chromosomal breakpoints have been reported in search of rearrangements: areas of high similarity, thermodynamic stability, composition and conformation of the DNA. Certain factors may influence chromosome breaks and are capable of predicting the propensity towards these types of events. These findings may be useful in the design of molecular techniques able to detect these changes in ALL. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  1. Altered neutrophil immunophenotypes in childhood B-cell precursor acute lymphoblastic leukemia

    Science.gov (United States)

    Oliveira, Elen; Bacelar, Thiago S.; Ciudad, Juana; Ribeiro, Maria Cecília M.; Garcia, Daniela R.N.; Sedek, Lukasz; Maia, Simone F.; Aranha, Daniel B.; Machado, Indyara C.; Ikeda, Arissa; Baglioli, Bianca F.; Lopez-Duarte, Nathalia; Teixeira, Lisandra A. C.; Szczepanski, Tomasz; Silva, Maria Luiza M.; Land, Marcelo G.P.

    2016-01-01

    An increasing number of evidences suggest a genetic predisposition in acute lymphoblastic leukemia (ALL) that might favor the occurrence of the driver genetic alterations. Such genetic background might also translate into phenotypic alterations of residual hematopoietic cells. Whether such phenotypic alterations are present in bone marrow (BM) cells from childhood B-cell precursor (BCP)-ALL remains to be investigated. Here we analyzed the immunophenotypic profile of BM and peripheral blood (PB) maturing/matured neutrophils from 118 children with BCP-ALL and their relationship with the features of the disease. Our results showed altered neutrophil phenotypes in most (77%) BCP-ALL cases. The most frequently altered marker was CD10 (53%), followed by CD33 (34%), CD13 (15%), CD15/CD65 (10%) and CD123 (7%). Of note, patients with altered neutrophil phenotypes had younger age (p = 0.03) and lower percentages of BM maturing neutrophils (p = 0.004) together with greater BM lymphocyte (p = 0.04), and mature B-cell (p = 0.03) counts. No significant association was found between an altered neutrophil phenotype and other disease features. These findings point out the potential existence of an altered residual hematopoiesis in most childhood BCP-ALL cases. PMID:27028865

  2. [Copy number alterations in adult patients with mature B acute lymphoblastic leukemia treated with specific immunochemotherapy].

    Science.gov (United States)

    Ribera, Jordi; Zamora, Lurdes; García, Olga; Hernández-Rivas, Jesús-María; Genescà, Eulàlia; Ribera, Josep-Maria

    2016-12-02

    Unlike Burkitt lymphoma, molecular abnormalities other than C-MYC rearrangements have scarcely been studied in patients with mature B acute lymphoblastic leukemia (B-ALL). The aim of this study was to analyze the frequency and prognostic significance of copy number alterations (CNA) in genes involved in lymphoid differentiation, cell cycle and tumor suppression in adult patients with B-ALL. We have analyzed by multiplex ligation-dependent probe amplification the genetic material from bone marrow at diagnosis from 25 adult B-ALL patients treated with rituximab and specific chemotherapy. The most frequent CNA were alterations in the 14q32.33 region (11 cases, 44%) followed by alterations in the cell cycle regulator genes CDKN2A/B and RB1 (16%). No correlation between the presence of specific CNA and the clinical-biologic features or the response to therapy was found. The high frequency of CNA in the 14q32.33 region, CDKN2A/B and RB1 found in our study could contribute to the aggressiveness and invasiveness of mature B-ALL. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  3. Proteomic changes in a childhood acute lymphoblastic leukemia cell line during the adaptation to vincristine.

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    Guzmán-Ortiz, Ana Laura; Aparicio-Ozores, Gerardo; Valle-Rios, Ricardo; Medina-Contreras, Oscar; Patiño-López, Genaro; Quezada, Héctor

    Relapse occurs in approximately 20% of Mexican patients with childhood acute lymphoblastic leukemia (ALL). In this group, chemoresistance may be one of the biggest challenges. An overview of complex cellular processes like drug tolerance can be achieved with proteomic studies. The B-lineage pediatric ALL cell line CCRF-SB was gradually exposed to the chemotherapeutic vincristine until proliferation was observed at 6nM, control cells were cultured in the absence of vincristine. The proteome from each group was analyzed by nanoHPLC coupled to an ESI-ion trap mass spectrometer. The identified proteins were grouped into overrepresented functional categories with the PANTHER classification system. We found 135 proteins exclusively expressed in the presence of vincristine. The most represented functional categories were: Toll receptor signaling pathway, Ras Pathway, B and T cell activation, CCKR signaling map, cytokine-mediated signaling pathway, and oxidative phosphorylation. Our study indicates that signal transduction and mitochondrial ATP production are essential during adaptation of leukemic cells to vincristine, these processes represent potential therapeutic targets. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  4. Tumor suppressive function of microRNA-192 in acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Mahtab Sayadi

    2017-08-01

    Full Text Available Non-coding RNAs play a critical role in gene regulation in cancer cells. Reduced expression of microRNA-192 (miR-192 has been detected in many cancers. In this study, we investigated the role of miR-192 in cell proliferation and cell cycle control in NALM-6 cell line, a model of acute lymphoblastic leukemia (ALL. Cell cycle analysis by DNA content using propidium iodide staining and cell apoptosis analysis using Annexin V assay were carried out. Cell proliferation changes were monitored using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. In addition, the relative changes in P53, BAX, CASP3, and BCL-2 gene expression were determined by quantitative reverse transcription PCR. Overexpression of miR-192 resulted in cell proliferation arrest in ALL cells. After 72 and 96 hours of transduction, apoptosis was significantly increased in the cells transduced with miR-192-overexpressing virus compared with control cells. The expression of P53, BAX, and CASP3 increased after 48 hours of transduction in miR-192-overexpressing cells, but no change was observed in BCL-2 expression. The G0/S and G1/S ratio changed to 7.5 and 4.5, respectively, in the cells overexpressing miR-192 compared with controls. The results of our study suggest, for the first time, tumor suppressive effects of miR-192 in ALL cells.

  5. Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles

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    Yanara Marincevic-Zuniga

    2017-08-01

    Full Text Available Abstract Background Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL. In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts. Methods We combined fusion gene detection with genome-wide DNA methylation analysis, gene expression profiling, and targeted sequencing to determine molecular signatures of emerging ALL subtypes. Results We identified 64 unique fusion events distributed among 80 individual patients, of which over 50% have not previously been reported in ALL. Although the majority of the fusion genes were found only in a single patient, we identified several recurrent fusion gene families defined by promiscuous fusion gene partners, such as ETV6, RUNX1, PAX5, and ZNF384, or recurrent fusion genes, such as DUX4-IGH. Our data show that patients harboring these fusion genes displayed characteristic genome-wide DNA methylation and gene expression signatures in addition to distinct patterns in single nucleotide variants and recurrent copy number alterations. Conclusion Our study delineates the fusion gene landscape in pediatric ALL, including both known and novel fusion genes, and highlights fusion gene families with shared molecular etiologies, which may provide additional information for prognosis and therapeutic options in the future.

  6. The Promise of Pharmacogenomics in Reducing Toxicity During Acute Lymphoblastic Leukemia Maintenance Treatment

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    Shoshana Rudin

    2017-04-01

    Full Text Available Pediatric acute lymphoblastic leukemia (ALL affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2–3 years. While the primary drugs used in the maintenance phase, 6-mercaptopurine (6-MP and methotrexate (MTX, are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity. For both drugs, pharmacogenomic factors have been identified that could explain a large amount of the variance in toxicity between patients, and may serve as effective predictors of toxicity during the maintenance phase of ALL treatment. 6-MP toxicity is associated with polymorphisms in the genes encoding thiopurine methyltransferase (TPMT, nudix hydrolase 15 (NUDT15, and potentially inosine triphosphatase (ITPA, which vary between ethnic groups. Moreover, MTX toxicity is associated with polymorphisms in genes encoding solute carrier organic anion transporter family member 1B1 (SLCO1B1 and dihydrofolate reductase (DHFR. Additional polymorphisms potentially associated with toxicities for MTX have also been identified, including those in the genes encoding solute carrier family 19 member 1 (SLC19A1 and thymidylate synthetase (TYMS, but their contributions have not yet been well quantified. It is clear that pharmacogenomics should be incorporated as a dosage-calibrating tool in pediatric ALL treatment in order to predict and minimize the occurrence of serious toxicities for these patients.

  7. Clinicopathologic Effect of DNMT3A Mutation in Adult T-Cell Acute Lymphoblastic Leukemia.

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    Aref, Salah; El Menshawy, Nadia; El-Ghonemy, Mohamed Sabry; Zeid, Tarek Abou; El-Baiomy, Mohamed Ali

    2016-01-01

    The present study aimed to determine the frequencies and clinicopathologic effect of a DNMT3A [DNA (cytosine-5)-methyltransferase 3A] mutation in patients with adult T-cell acute lymphoblastic leukemia (T-ALL). A total of 64 patients with T-ALL who had been admitted to Mansoura University Oncology Center were included in the present study. For all patients, DNA extraction and amplification with sequencing analysis using the 310 ABI genetic analyzer for detection of a mutation (R882H). The DNMT3A mutation (R882H) was found in 12 of the 64 patients (18.8%). The DNMT3A mutation was frequently detected in the older age group and was associated with high leukocytic counts, a high bone marrow blast cell percentage, and the frequent presence of extramedullary disease. However, it was not associated with the hemoglobin level, red blood cell count, or platelet count. The patients with mutant T-ALL had a low tendency to achieve remission after induction. These patients had significantly shorter overall survival and shorter disease-free survival compared with those with wild-type T-ALL (P = .037 and P = .006, respectively). DNMT3A is frequently mutated in T-ALL and is associated with distinct clinicopathologic entities and a poor prognosis. These findings could help in risk stratification and treatment decisions for patients with T-ALL. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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    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.

  9. Salivary microbial counts and buffer capacity in children with acute lymphoblastic leukemia.

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    Ou-Yang, Li-Wei; Chang, Pei-Ching; Tsai, Aileen I; Jaing, Tang-Her; Lin, Shiao-Yu

    2010-01-01

    The aim of this study was to evaluate the caries activity in children undergoing maintenance stage chemotherapy courses. Forty-six children with acute lymphoblastic leukemia (ALL) were examined, the age ranged from 3 to 12 years with a mean age of 7(1/2) years. They were under maintenance stage chemotherapy at the Department of Pediatric Hematology of Chang-Gung Memorial Hospital, Taoyuan, Taiwan. A control group of healthy children was recruited by age and sex-matching criteria. The children received only a clinical dental examination without radiographs. Decayed (D), Missing (M), and Filled (F) Tooth surfaces (S) scores were recorded following the WHO criteria. After oral examination, stimulated saliva samples were collected from the subjects to exam the salivary Streptococcus mutans counts, salivary lactobacilli counts and salivary buffer capacity. The Wilcoxon signed-rank test shows that the salivary Streptococcus mutans counts in ALL children were significantly lower than healthy subjects (Pbuffer capacity than the control group (P=.002). The mean DEFTS/DMFTS scores of the ALL group were higher than the control group, but the differences did not reach statistical significance. Specific oral prevention regimens for ALL children undergoing chemotherapy should be planned for patients with unusually low salivary buffer capacity.

  10. Methylenetetrahydrofolate reductase C677T and overall survival in pediatric acute lymphoblastic leukemia: a systematic review.

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    Ojha, Rohit P; Gurney, James G

    2014-01-01

    A summary of the evidence pertaining to the association between methylenetetrahydrofolate reductase (MTHFR) C677T and overall survival in pediatric acute lymphoblastic leukemia (ALL) is not currently available. We thus reviewed the literature on the association between MTFHR C677T and overall survival in pediatric ALL. We searched PubMed/MEDLINE, Scopus and ISI Web of Knowledge literature databases without language restrictions to identify observational studies among children diagnosed between ages 0 and 19 years that assessed MTHFR 677 polymorphisms in relation to ALL survival. We identified six studies comprising 909 pediatric patients with ALL. The magnitude of relative risk (RR) for pediatric ALL mortality varied by genotype comparison and study population, ranging from RR = 0.84 (95% confidence limits [CL]: 0.24, 3.0) for a TT vs. CT/CC comparison to RR = 7.0 (95% CL: 0.98, 49) for a TT vs. CC comparison. The current evidence suggests that individuals with MTHFR 677 variants (i.e. at least one T allele) may have a higher relative risk of pediatric ALL mortality, with greater statistical support for MTHFR 677TT. With more detailed supporting evidence, MTHFR 677 genotyping at diagnosis could provide an option for individualizing therapy and further reducing pediatric ALL mortality in certain populations.

  11. Idiotype as a tumor-specific marker in childhood B cell acute lymphoblastic leukemia.

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    Carroll, W L; Link, M P; Cleary, M L; Bologna, S; Carswell, C; Amylon, M D; Smith, S D; Levy, R

    1988-04-01

    Immunoglobulin (Ig) or idiotype (Id) is a tumor-specific target in those B cell malignancies that express this molecule on their surface. We explored the biology of B cell acute lymphoblastic leukemia (B cell ALL) using Id as a tumor marker. In this report we describe the development of anti-Id monoclonal antibodies (MAB) for two children with B cell ALL. These reagents were used retrospectively to study tumor kinetics and to detect residual disease after chemotherapy. In both cases serum Id values were strikingly high at diagnosis (1.2 mg/mL and 10.8 mg/mL), suggesting that the tumor cells were relatively mature B cells capable of significant antibody production. In both patients the serum Id levels fell with the institution of therapy and confirmed that the patients were in remission. Increasing serum Id predicted relapse four months before conventional methods in patient 1, and Id proved to be a more sensitive measure of tumor burden than Southern blot analysis of rearranged Ig genes in bone marrow samples. Surprisingly, low levels of Id were redetected in the second patient just before completing therapy and have persisted for over a year despite the absence of clinical evidence of recurrent disease. Thus, serum Id levels reflect tumor burden during initial therapy but may not necessarily predict tumor progression after a complete clinical remission.

  12. Approach to prediagnostic clinical semiology, noticed by mothers, of childhood acute lymphoblastic leukemia.

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    Castro-Jiménez, Miguel Ángel; Rueda-Arenas, Ernesto; Cabrera-Rodríguez, Daladier

    2015-08-01

    Recognizing early symptoms of acute lymphoblastic leukemia (ALL) may help to make an early diagnosis. The objective of this study is to identify clinical manifestations preceding the diagnosis of childhood ALL from the maternal perspective and to establish the time elapsed from the first manifestation to the diagnosis. Six hospitals located in Bogotá and Bucaramanga (Colombia) participated. Cases consisted of children under 15 years old with incidental diagnosis of ALL between January 2000 and March 2005. Data on sociodemographic characteristics, pre diagnostic clinical manifestations, first symptom, and time to diagnosis were collected during interviews with mothers. Medians, ranges and proportions were estimated. P values below 0.05 were considered significant. One hundred and twenty-eight cases were analyzed. Pallor (83.6%), loss of appetite (72.6%), weight loss (62.5%), andbleeding into the skin (39.1%) were the most common symptoms preceding diagnosis. The delay between the occurrence of the first symptom and the diagnosis of ALL depends on what the first manifestation is, and it maybe shorter when there is evidence of hemorrhage (median= 14 days). The presence of palpable lymph nodes in the armpits was more significant in girls than in boys (p= 0.04). Childhood ALL symptomatology in the prediagnostic stage is not specific to this disease; however, the clinical sign and time since its occurrence may serve as a guide in the early stage of this disease.

  13. The effects of dexamethasone on sleep in young children with acute lymphoblastic leukemia.

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    Rosen, Gerald; Harris, Anne K; Liu, Meixia; Dreyfus, Jill; Krueger, James; Messinger, Yoav H

    2015-04-01

    Corticosteroids, which are a mainstay in the treatment of acute lymphoblastic leukemia (ALL), have a well-documented adverse effect on sleep. We sought to characterize the effects of dexamethasone on sleep over an entire 28-day treatment cycle using actigraphy, an objective measure of sleep. The sleep of 25 children aged 2-9 years (mean 4.5 years) with ALL treated with dexamethasone were evaluated during maintenance chemotherapy using a within-subject experimental design, actigraphy, and standardized questionnaires to assess sleep, sleep problems, and fatigue. During the five days of dexamethasone treatment, sleep time increased during the night (535 vs. 498 min; p = 0.004) and daytime napping increased the following day (14 vs. 0 min; p = 0.002), and the number of wake episodes during the night was lower (14 vs. 20; p =  ≤ 0.001). However, when assessed individually, sleep-onset time, efficiency, and wake after sleep onset during the night were unchanged during dexamethasone treatment; when the cumulative effect of all of these factors was assessed, there was a statistically and clinically significant increase in nighttime sleep duration during dexamethasone treatment. During the five days of treatment with dexamethasone, an increase in nighttime sleep as well as daytime napping was observed in young children with ALL. The increases in sleep duration return to baseline one day after the discontinuation of dexamethasone. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Eating behavior during dexamethasone treatment in children with acute lymphoblastic leukemia.

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    Warris, Lidewij T; van den Akker, Erica L T; Bierings, Marc B; van den Bos, Cor; Aarsen, Femke K; Zwaan, Michel C; Tissing, Wim J E; Veening, Margreet A; Pieters, Rob; van den Heuvel-Eibrink, Marry M

    2017-12-01

    Large prospective studies on dexamethasone-induced changes in eating behavior, energy, and nutrient intake are lacking in pediatric acute lymphoblastic leukemia (ALL). We prospectively studied eating behavior, energy, nutrient intake, and the effect on leptin and adiponectin levels during dexamethasone administration in children with ALL. Parents of patients with ALL (3-16 years) completed a dietary diary for their child during 4 days of dexamethasone (6 mg/m(2) ) administration. Energy intake and nutrient intake (energy percentage = E%) were assessed and compared with the recommended intake. The Dutch Eating Behavior Questionnaire for Children was completed before start and after 4 days of dexamethasone administration by patients of 7-12 years of age. Fasting leptin and adiponectin levels were also measured before start and after 4 days of dexamethasone administration. Energy intake per day(kcal) (N = 44) increased significantly during dexamethasone (median day 1: 1,103 (717-1,572) versus day 4: 1,482 (1,176-1,822), P dexamethasone significantly decreased restrained eating (P = 0.04). Leptin levels as well as adiponectin levels increased significantly during the dexamethasone course. Four days of dexamethasone treatment significantly increased energy intake, including excessive saturated fat and salt intake, and changed eating behavior in children with ALL. Nutritional and behavioral interventions during dexamethasone treatment are recommended to stimulate a healthy lifestyle. © 2017 Wiley Periodicals, Inc.

  15. Effects of Malnutrition on Neutrophil/Mononuclear Cell Apoptotic Functions in Children with Acute Lymphoblastic Leukemia.

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    Cakir, Fatma Betul; Berrak, Su Gülsün; Aydogan, Gonul; Tulunay, Aysin; Timur, Cetin; Canpolat, Cengiz; Eksioglu Demiralp, Emel

    2017-04-01

    Recent studies claim that apoptosis may explain immune dysfunction observed in malnutrition. The objective of this study was to determine the effect of malnutrition on apoptotic functions of phagocytic cells in acute lymphoblastic leukemia (ALL). Twenty-eight ALL patients (13 with malnutrition) and thirty controls were enrolled. Neutrophil and mononuclear cell apoptosis of ALL patients and the control group were studied on admission before chemotherapy and repeated at a minimum of three months after induction of chemotherapy or when the nutritional status of leukemic children improved. The apoptotic functions of both ALL groups on admission were significantly lower than those of the control group. The apoptotic functions were lower in ALL patients with malnutrition than those in ALL patients without malnutrition, but this was not statistically significant. The repeated apoptotic functions of both ALL groups were increased to similar values with the control group. This increase was found to be statistically significant. The apoptotic functions in ALL patients were not found to be affected by malnutrition. However, after dietary intervention, increased apoptotic functions in both ALL patient groups deserve mentioning. Dietary intervention should always be recommended as malnutrition or cachexia leads to multiple complications. Enhanced apoptosis might originate also from remission state of cancer.

  16. Influence of Musculoskeletal Manifestations as the Only Presenting Symptom in B-Cell Acute Lymphoblastic Leukemia.

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    Kang, Seungcheol; Im, Ho Joon; Bae, Kunhyung; Park, Soo-Sung

    2017-03-01

    To evaluate the clinical and prognostic impact of musculoskeletal manifestations as the only initial presenting symptom in childhood acute lymphoblastic leukemia (ALL). We retrospectively reviewed 158 children with precursor B-cell type ALL who were followed up for >2 years. The patients were assigned to the groups musculoskeletal manifestations (n = 24) or nonmusculoskeletal manifestations (n = 134) based on initial presenting symptom. The symptom duration (regarding any initial presenting symptom) and the leukemic symptom duration (regarding symptoms of systemic manifestation, such as fever, bleeding, or pallor) were assessed, along with other clinical characteristics. The musculoskeletal manifestations group exhibited a longer symptom duration than the nonmusculoskeletal manifestations group (43 days vs 22 days, P = .006), but overall survival did not significantly differ between the groups. Multivariate analysis indicated that a longer symptom duration did not affect prognosis but that a longer leukemic symptom duration was associated with a poorer prognosis (hazard ratio, 7.720; P = .048). Musculoskeletal manifestations are associated significantly with diagnostic delay, but this delay does not affect the prognosis. Diagnostic delay after the onset of leukemic symptoms, however, does appear to affect the prognosis. Intensive evaluations for hematologic malignancies may be unnecessary in children who complain of limb pain without any definite cause, unless they also present with accompanying leukemic symptoms. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. ROLE OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN ADULT PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

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    Federico Lussana

    2014-10-01

    Full Text Available Adult acute lymphoblastic leukemia (ALL is a heterogeneous disease, due to the expression of different biological and clinical risk factors, for which allogeneic stem cell transplantation (alloHSCT is an effective consolidation therapy. The non-relapse mortality of alloHSCT remains significantly higher compared with that of conventional chemotherapy; therefore, one of the main challenges in the care of ALL is to establish a more precise prognostic definition to select patients who could take advantage from an alloHSCT. Currently, the use of minimal residual disease following induction and early consolidation therapy has improved the prognostic accuracy in defining ALL risk class. In Philadelphia-positive ALL, the introduction of tyrosine kinase inhibitors pre and post alloHSCT appears to improve outcomes significantly and, in the absence of specifically designed clinical trials, alloHSCT remains the most effective post- remission therapy. Nowadays, alloHSCT can be performed according to different modalities encompassing the use of different conditioning regimens, as well as different donors and stem cell source, with a significant accessibility to transplant.

  18. The association between Acute Lymphoblastic Leukemia in children and Helicobacter pylori as the marker for sanitation

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    Hishamuddin Pengiran

    2012-07-01

    Full Text Available Abstract Background Greaves “delayed infection” hypothesis suggested that Acute Lymphoblastic Leukemia (ALL in children is caused by a lack of exposure to infection in infancy, which may be due higher standards of sanitation. We have conducted an ecologic analysis of the relationship between sanitation, using Helicobacter pylori (H. pylori as the marker, and the incidence of childhood ALL in 127 cancer registries from 28 countries. Results There were inverse associations between H. pylori prevalence and ALL incidence rates in children. These associations were minor and only significant for ALL incidence rates for all cancer registries. They became non-significant and smaller in magnitude when the population source and/or the GNP per capita were added to the relationship. Furthermore, these results were unchanged when the associations were examined using the Generalized Estimating Equations. Conclusions Although the findings showed lower prevalence of H. pylori and improved sanitation is associated with increased incidence of childhood ALL, they do not conclusively support Greaves “delayed infection” hypothesis.

  19. Motor nervous system impairment persists in long-term survivors of childhood acute lymphoblastic leukemia.

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    Lehtinen, Satu S; Huuskonen, Usko E; Harila-Saari, Arja H; Tolonen, Uolevi; Vainionpää, Leena K; Lanning, B Marjatta

    2002-05-01

    The objective of the current study was to determine whether therapy for childhood acute lymphoblastic leukemia (ALL) results in long-lasting neurologic signs or electrophysiologic injuries within the motor tracts. Twenty-seven children who were treated for ALL were studied clinically 5 years after the cessation of therapy by means of motor-evoked potentials (MEPs) elicited by magnetic stimulation transcranially and peripherally. An equal number of healthy children matched with regard to age, gender, and height served as the control group. The MEP latencies to the hands and legs elicited by stimulation at the cortex were prolonged significantly in the children treated for ALL compared with the control group, with the differences being 2.2 milliseconds [ms] (P motor difficulties and dysdiadochokinesia. Neurologic signs still persisted 5 years after therapy for ALL. Approximately 33% of the patients had fine or gross motor difficulties and dysdiadochokinesia, and demyelinative injuries to the peripheral nerve tracts were found proximally but not within the central nervous system. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10503

  20. Preparation of Primary Acute Lymphoblastic Leukemia Cells in Different Cell Cycle Phases by Centrifugal Elutriation.

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    Delgado, Magdalena; Kothari, Anisha; Hittelman, Walter N; Chambers, Timothy C

    2017-11-10

    The ability to synchronize cells has been central to advancing our understanding of cell cycle regulation. Common techniques employed include serum deprivation; chemicals which arrest cells at different cell cycle phases; or the use of mitotic shake-off which exploits their reduced adherence. However, all of these have disadvantages. For example, serum starvation works well for normal cells but less well for tumor cells with compromised cell cycle checkpoints due to oncogene activation or tumor suppressor loss. Similarly, chemically-treated cell populations can harbor drug-induced damage and show stress-related alterations. A technique which circumvents these problems is counterflow centrifugal elutriation (CCE), where cells are subjected to two opposing forces, centrifugal force and fluid velocity, which results in the separation of cells on the basis of size and density. Since cells advancing through the cycle typically enlarge, CCE can be used to separate cells into different cell cycle phases. Here we apply this technique to primary acute lymphoblastic leukemia cells. Under optimal conditions, an essentially pure population of cells in G1 phase and a highly enriched population of cells in G2/M phases can be obtained in excellent yield. These cell populations are ideally suited for studying cell cycle-dependent mechanisms of action of anticancer drugs and for other applications. We also show how modifications to the standard procedure can result in suboptimal performance and discuss the limitations of the technique. The detailed methodology presented should facilitate application and exploration of the technique to other types of cells.

  1. Childhood acute lymphoblastic leukemia in Turkey: factors influencing treatment and outcome: a single center experience.

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    Hazar, Volkan; Karasu, Gulsun Tezcan; Uygun, Vedat; Akcan, Mediha; Küpesiz, Alphan; Yesilipek, Akif

    2010-11-01

    There is limited data about the long-term treatment outcome and prognosis of childhood acute lymphoblastic leukemia (ALL) in developing countries. Our study was designed to assess survival data and identify risk factors. Data of 142 children with ALL who were treated with a modified BFM 95 protocol between 1997 and 2007 were evaluated. The median age was 4.3 years. Complete remission (CR) rate after induction phase was 93.5%; with 2.1% induction-related mortality and 0.7% having resistance disease. Of complete responders, 67.1% are in continuous CR with a median follow-up of 63 months (range: 24 to 153 mo). Treatment-related mortality was 17.7% and the total rate of treatment abandonment was 3.5%. The probability of event-free survival was 67.3% (95% confidence interval 59.3-75.3) at 4 years and 63.2% (95% confidence interval 54.4-72.0) at 8 years. This report examines children with ALL treated with a modified ALL-BFM 95 protocol in a tertiary care center in Turkey with adequate follow up and demonstrates the need for improvements especially for patients with unfavorable risk group and strategies to reduce deaths from infection in CR to keep pace with cure rates in developed countries.

  2. Modeling the Mechanism of GR/c-Jun/Erg Crosstalk in Apoptosis of Acute Lymphoblastic Leukemia.

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    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.

  3. Parental Perceptions of Obesity and Obesity Risk Associated With Childhood Acute Lymphoblastic Leukemia.

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    Jones, Gary L; McClellan, Wendy; Raman, Sripriya; Sherman, Ashley; Guest, Erin; August, Keith

    2017-07-01

    The prevalence of obesity and related comorbidities in survivors of childhood acute lymphoblastic leukemia (ALL) is well established and ranges anywhere from 29% to 69% depending on the study. We sought to explore the awareness of parents of survivors of childhood ALL regarding the increased risk of obesity and their perceptions regarding the overall health of their child. One hundred twenty-one parents of 99 survivors of pediatric ALL completed surveys regarding perceptions of obesity risk in survivors. Eighty percent of parents of overweight and obese survivors correctly identified their child as "a little overweight" or "overweight." Few parents recalled discussing weight gain (21%) or obesity risk (36%) with their practitioner. Parents that did recall having these discussions and/or reported a decreased level of posttherapy activity in their child were more likely to be concerned about their child's weight status. Improved awareness and education regarding the risk of obesity and associated comorbid conditions may provide an avenue for future prevention of obesity in survivors of pediatric ALL. Discussion and education regarding a healthy lifestyle, including proper diet and exercise, should be incorporated early in routine patient visits.

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

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    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.

  5. Age and leukocyte count as prognostic factors on acute lymphoblastic leukemia: hgmlal07 cohort

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    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.

  6. Trajectories of Obesity and Overweight Rates Among Survivors of Childhood Acute Lymphoblastic Leukemia.

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    Winkler, Megan R; Hockenberry, Marilyn J; McCarthy, Kathy S; Silva, Susan G

    2015-07-01

    To describe the trajectories of obesity/overweight rates by age group among survivors of childhood acute lymphoblastic leukemia (ALL) from diagnosis through several years post-therapy. Longitudinal, descriptive. Hematology/oncology clinic in the southwestern United States. 62 child and adolescent ALL survivors receiving treatment and follow-up care from 1999-2013. Retrospective chart review of height, weight, and body mass index. Annual obesity/overweight rates and developmental age groups. Different trajectories of obesity/overweight rates existed among age groups. Forty-seven percent of adolescents met the Centers for Disease Control and Prevention criteria for obesity/overweight status at some point following diagnosis, compared to 68% of school-age and 73% of preschool children. Preschool children demonstrated the most rapid rate increase following diagnosis, with a particularly susceptible period in the years immediately following therapy. Obesity/overweight persistence was most characteristic of school-age children. Important variations in rate and pattern of weight status trajectories exist by age group, demonstrating that children diagnosed with ALL during the preschool and school-age developmental years have the greatest vulnerability of developing obesity/overweight status. Obesity/overweight prevention efforts are greatly needed in children with ALL, and efforts should occur before ALL treatment completion in preschool and school-age children.

  7. Oral manifestations during chemotherapy for acute lymphoblastic leukemia: a case report.

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    Gomes, Mônica Fernandes; Kohlemann, Katya Rodrigues; Plens, Glauco; Silva, Marcelo Milone; Pontes, Elitânia Marinho; da Rocha, João Carlos

    2005-04-01

    A 14-year-old, male patient was referred for the treatment of mucositis, idiopathic facial asymmetry, and candidiasis. The patient had been undergoing chemotherapy for 5 years for acute lymphoblastic leukemia. He presented with a swollen face, fever, and generalized symptomatology in the mouth with burning. On physical examination, general signs of poor health, paleness, malnutrition, and jaundice were observed. The extraoral clinical examination showed edema on the right side of the face and cutaneous erythema. On intraoral clinical examination, generalized ulcers with extensive necrosis on the hard palate mucosa were observed, extending to the posterior region. Both free and attached gingivae were ulcerated and edematous with exudation and spontaneous bleeding, mainly in the superior and inferior anterior teeth region. The tongue had no papillae and was coated, due to poor oral hygiene. The patient also presented with carious white lesions and enamel hypoplasia, mouth opening limitation, and foul odor. After exfoliative cytology of the affected areas, the diagnosis was mixed infection by Candida albicans and bacteria. Recommended treatment was antibiotics and antifungal administration, periodontal prophylaxis, topical application of fluor 1.23%, and orientation on and control of proper oral hygiene and diet during the remission phase of the disease.

  8. Pten mediates Myc oncogene dependence in a conditional zebrafish model of T cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Gutierrez, Alejandro; Grebliunaite, Ruta; Feng, Hui; Kozakewich, Elena; Zhu, Shizhen; Guo, Feng; Payne, Elspeth; Mansour, Marc; Dahlberg, Suzanne E; Neuberg, Donna S; den Hertog, Jeroen; Prochownik, Edward V; Testa, Joseph R; Harris, Marian; Kanki, John P; Look, A Thomas

    2011-08-01

    The MYC oncogenic transcription factor is overexpressed in most human cases of T cell acute lymphoblastic leukemia (T-ALL), often downstream of mutational NOTCH1 activation. Genetic alterations in the PTEN-PI3K-AKT pathway are also common in T-ALL. We generated a conditional zebrafish model of T-ALL in which 4-hydroxytamoxifen (4HT) treatment induces MYC activation and disease, and withdrawal of 4HT results in T-ALL apoptosis and tumor regression. However, we found that loss-of-function mutations in zebrafish pten genes, or expression of a constitutively active Akt2 transgene, rendered tumors independent of the MYC oncogene and promoted disease progression after 4HT withdrawal. Moreover, MYC suppresses pten mRNA levels, suggesting that Akt pathway activation downstream of MYC promotes tumor progression. Our findings indicate that Akt pathway activation is sufficient for tumor maintenance in this model, even after loss of survival signals driven by the MYC oncogene.

  9. PEGging down risk factors for peg-asparaginase hepatotoxicity in patients with acute lymphoblastic leukemia †.

    Science.gov (United States)

    Rausch, Caitlin R; Marini, Bernard L; Benitez, Lydia L; Elias, Allison; Burke, Patrick W; Bixby, Dale; Perissinotti, Anthony J

    2017-07-18

    Asparaginase is commonly de-emphasized/omitted in adult acute lymphoblastic leukemia regimens due to poor tolerability, including hepatotoxicity (HTX). Adult patients (n = 100) given induction therapy containing pegylated asparaginase (PEG) from January 2008 to February 2016 were evaluated for HTX. Sixteen patients met criteria for HTX (direct bilirubin >3 g/dL). A multivariable model identified body surface area >2m2 (OR 7.40; 95% CI: 1.73-31.61, p = .007), albumin <3 mg/dL (OR 4.62; 95% CI: 1.09-19.68, p = .038), and platelet count <50 K/mm3 (OR 9.36; 95% CI: 2.13-41.17, p = .003) as risk factors for HTX. More patients with HTX missed ≥1 dose of intended chemotherapy (75% vs. 8%, p < .001). In patients with HTX, complete response and 30-day mortality rates were 40% and 9% versus 73% and 1% in patients without HTX (p = .02 and p < .001). A risk scoring tool was created to predict risk of toxicity, which should be validated through a prospective evaluation.

  10. 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. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  11. Oxidative DNA base damage and antioxidant enzyme levels in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Sentürker, S; Karahalil, B; Inal, M; Yilmaz, H; Müslümanoglu, H; Gedikoglu, G; Dizdaroglu, M

    1997-10-27

    We have investigated the levels of several antioxidant enzymes and the level of oxidative DNA base damage in lymphocytes of children with acute lymphoblastic leukemia (ALL) and in disease-free children. Children with ALL had just been diagnosed with the disease and had received no therapy prior to obtaining blood samples. A multitude of typical hydroxyl radical-induced base lesions in lymphocyte DNA of children were identified and quantified by gas chromatography-isotope dilution mass spectrometry. Higher levels of DNA base lesions were observed in patients with ALL than in children without the disease. The levels of the antioxidant enzymes glutathione peroxidase, catalase and superoxide dismutase in lymphocytes of ALL patients were lower than in lymphocytes of controls. These findings are in agreement with earlier observations in various types of adulthood cancer. Some of the identified DNA base lesions are known to possess premutagenic properties and may play a role in carcinogenesis. The results may indicate a possible link between decreased activities of antioxidant enzymes and increased levels of DNA base lesions due to oxidative damage, and support the notion that free radical reactions may be increased in malignant cells.

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

    Directory of Open Access Journals (Sweden)

    Emine Guven Maiorov

    2013-01-01

    Full Text Available T-cell acute lymphoblastic leukemia (T-ALL is a complex disease, resulting from proliferation of differentially arrested immature T cells. The molecular mechanisms and the genes involved in the generation of T-ALL remain largely undefined. In this study, we propose a set of genes to differentiate individuals with T-ALL from the nonleukemia/healthy ones and genes that are not differential themselves but interconnected with highly differentially expressed ones. We provide new suggestions for pathways involved in the cause of T-ALL and show that network-based classification techniques produce fewer genes with more meaningful and successful results than expression-based approaches. We have identified 19 significant subnetworks, containing 102 genes. The classification/prediction accuracies of subnetworks are considerably high, as high as 98%. Subnetworks contain 6 nondifferentially expressed genes, which could potentially participate in pathogenesis of T-ALL. Although these genes are not differential, they may serve as biomarkers if their loss/gain of function contributes to generation of T-ALL via SNPs. We conclude that transcription factors, zinc-ion-binding proteins, and tyrosine kinases are the important protein families to trigger T-ALL. These potential disease-causing genes in our subnetworks may serve as biomarkers, alternative to the traditional ones used for the diagnosis of T-ALL, and help understand the pathogenesis of the disease.

  13. Letter regarding Zhao et al. entitled " DPYD gene polymorphisms are associated with risk and chemotherapy prognosis in pediatric patients with acute lymphoblastic leukemia".

    Science.gov (United States)

    Deenen, Maarten J; Henricks, Linda M; Sonke, Gabe S; Schellens, Jan Hm; Meulendijks, Didier

    2017-06-01

    Zhao et al. investigated the association between germline genetic polymorphisms in DPYD, the gene encoding dihydropyrimidine dehydrogenase, and (1) the risk of developing pediatric acute lymphoblastic leukemia and (2) outcome of acute lymphoblastic leukemia following the treatment with 5-fluorouracil plus oxaliplatin (FOLFOX). The authors found that the common DPYD variant c.85T>C (rs1801265, DPYD*9A) was significantly associated with (1) risk of developing pediatric acute lymphoblastic leukemia, (2) complete response rate, (3) event-free survival, and (4) treatment-related toxicity. The authors conclude that patients carrying the c.85T>C C allele have an increased risk of developing acute lymphoblastic leukemia and have inferior outcome, and that DPYD c.85T>C can be used as a guide for individualized treatment and the decision to utilize 5-fluorouracil in acute lymphoblastic leukemia patients. In our view, the published article gives rise to multiple critical issues regarding the study's rationale and the methodology used, which strongly question the validity of the authors' conclusions.

  14. Early life exposure to infections and risk of childhood acute lymphoblastic leukemia

    Science.gov (United States)

    Urayama, Kevin Y.; Ma, Xiaomei; Selvin, Steve; Metayer, Catherine; Chokkalingam, Anand P.; Wiemels, Joseph L.; Does, Monique; Chang, Jeffrey; Wong, Alan; Trachtenberg, Elizabeth; Buffler, Patricia A.

    2011-01-01

    Evidence from a growing number of studies indicates that exposure to common infections early in life may be protective against childhood acute lymphoblastic leukemia (ALL). We examined the relationship between three measures of early life exposure to infections—daycare attendance, birth order and common childhood infections in infancy—with the risk of ALL in non-Hispanic white and Hispanic children, two ethnicities that show sociodemographic differences. The analysis included 669 ALL cases (284 non-Hispanic whites and 385 Hispanics) and 977 controls (458 non-Hispanic whites and 519 Hispanics) ages 1–14 years enrolled in the Northern California Childhood Leukemia Study (NCCLS). When the three measures were evaluated separately, daycare attendance by the age of 6 months (odds ratio [OR] for each thousand child-hours of exposure = 0.90, 95% confidence interval [CI]: 0.82–1.00) and birth order (OR for having an older sibling = 0.68, 95% CI: 0.50–0.92) were associated with a reduced risk of ALL among non-Hispanic white children but not Hispanic children, whereas ear infection before age 6 months was protective in both ethnic groups. When the three measures were assessed simultaneously, the influence of daycare attendance (OR = 0.83, 95% CI: 0.73–0.94) and having an older sibling (OR = 0.59, 95% CI: 0.43–0.83) became stronger for non-Hispanic white children. In Hispanic children, a strong reduction in risk associated with ear infections persisted (OR = 0.45, 95% CI: 0.25–0.79). Evidence of a protective role for infection-related exposures early in life is supported by findings in both the non-Hispanic white and Hispanic populations within the NCCLS. PMID:21280034

  15. Current Concepts in Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Bernt, Kathrin M.; Hunger, Stephen P.

    2014-01-01

    The t(9;22)(q34;q11) or Philadelphia chromosome creates a BCR–ABL1 fusion gene encoding for a chimeric BCR–ABL1 protein. It is present in 3–4% of pediatric acute lymphoblastic leukemia (Ph+ ALL), and about 25% of adult ALL cases. Prior to the advent of tyrosine kinase inhibitors (TKI), Ph+ ALL was associated with a very poor prognosis despite the use of intensive chemotherapy and frequently hematopoietic stem-cell transplantation (HSCT) in first remission. The development of TKIs revolutionized the therapy of Ph+ ALL. Addition of the first generation ABL1 class TKI imatinib to intensive chemotherapy dramatically increased the survival for children with Ph+ ALL and established that many patients can be cured without HSCT. In parallel, the mechanistic understanding of Ph+ ALL expanded exponentially through careful mapping of pathways downstream of BCR–ABL1, the discovery of mutations in master regulators of B-cell development such as IKZF1 (Ikaros), PAX5, and early B-cell factor (EBF), the recognition of the complex clonal architecture of Ph+ ALL, and the delineation of genomic, epigenetic, and signaling abnormalities contributing to relapse and resistance. Still, many important basic and clinical questions remain unanswered. Current clinical trials are testing second generation TKIs in patients with newly diagnosed Ph+ ALL. Neither the optimal duration of therapy nor the optimal chemotherapy backbone are currently defined. The role of HSCT in first remission and post-transplant TKI therapy also require further study. In addition, it will be crucial to continue to dig deeper into understanding Ph+ ALL at a mechanistic level, and translate findings into complementary targeted approaches. Expanding targeted therapies hold great promise to decrease toxicity and improve survival in this high-risk disease, which provides a paradigm for how targeted therapies can be incorporated into treatment of other high-risk leukemias. PMID:24724051

  16. Involvement of MTHFR and TPMT genes in susceptibility to childhood acute lymphoblastic leukemia (ALL) in Mexicans.

    Science.gov (United States)

    Gutiérrez-Álvarez, Ossyneidee; Lares-Asseff, Ismael; Galaviz-Hernández, Carlos; Reyes-Espinoza, Elio-Aarón; Almanza-Reyes, Horacio; Sosa-Macías, Martha; Chairez Hernández, Isaías; Salas-Pacheco, José-Manuel; Bailón-Soto, Claudia E

    2016-03-01

    Folate metabolism plays an essential role in the processes of DNA synthesis and methylation. Deviations in the folate flux resulting from single-nucleotide polymorphisms in genes encoding folate-dependent enzymes may affect the susceptibility to leukemia. This case-control study aimed to assess associations among MTHFR (C677T, A1298C) and TPMT (*2, *3A) mutations as well as to evaluate the synergistic effects of combined genotypes for both genes. Therefore, these genetic variants may lead to childhood acute lymphoblastic leukemia (ALL) susceptibility, in a Mexican population study. DNA samples obtained from 70 children with ALL and 152 age-matched controls (range, 1-15 years) were analyzed by real-time reverse transcription polymerase chain reaction (RT-qPCR) to detect MTHFR C677T and A1298C and TPMT*2 and TPMT*3A genotypes. The frequency of the MTHFR A1298C CC genotype was statistically significant (odds ratio [OR], 6.48; 95% 95% confidence intervals [CI], 1.26-33.2; p=0.025). In addition, the combined 677CC+1298AC genotype exhibited a statistically significant result (OR, 0.23; 95% CI, 0.06-0.82; p=0.023). No significant results were obtained from the MTHFR (C677T CT, C677T TT) or TPMT (*2, *3A) genotypes. More importantly, no association between the synergistic effects of either gene (MTHFR and/or TPMT) and susceptibility to ALL was found. The MTHFR A1298C CC genotype was associated with an increased risk of developing childhood ALL. However, a decreased risk to ALL with the combination of MTHFR 677CC+1298AC genotypes was found.

  17. Tobacco Smoke and Ras Mutations Among Latino and Non-Latino Children with Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Kaur, Maneet; de Smith, Adam J; Selvin, Steve; Zhang, Luoping; Cunningham, Marc; Kang, Michelle W; Hansen, Helen M; Cooper, Robert M; McKean-Cowdin, Roberta; Wiemels, Joseph L; Metayer, Catherine

    2016-11-01

    Childhood acute lymphoblastic leukemia (ALL) is a biologically heterogeneous disease, and mutations in the KRAS and NRAS oncogenes are present at diagnosis in about one-fifth of cases. Ras mutations were previously associated with environmental exposures in leukemias as well as in many other cancer types. This study examined whether Ras mutation could define a unique etiologic group of childhood ALL associated with tobacco smoke, a well-established mutagen and carcinogen. We included 670 children with ALL enrolled in a case-control study in California (1995-2013), including 50.6% Latinos. Parental and child exposure to tobacco smoke was obtained from interviews. Sanger sequencing was used to detect the common KRAS and NRAS hotspot mutations in diagnostic bone marrow DNA. ALL cases were also characterized for common chromosome abnormalities. In case-case analyses, logistic regression analyses were used to estimate odds ratios to describe the association between tobacco smoke exposure and childhood ALL with Ras mutations. KRAS or NRAS mutations were detected in ∼18% of children diagnosed with ALL. Ras mutations were more common among Latino cases compared with non-Latino whites and in high-hyperdiploid ALL. No associations were observed between parental smoking or child's passive exposure to smoke and Ras positive ALL. The apparent lack of association between tobacco smoke and Ras mutation in childhood ALL suggests that Ras mutations do not specifically define a tobacco-related etiologic pathway. Reasons for racial and ethnic differences in ALL are not well understood and could reflect differences in etiology that warrant further examination. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  18. EZH2 mutations and promoter hypermethylation in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Schäfer, Vivien; Ernst, Jana; Rinke, Jenny; Winkelmann, Nils; Beck, James F; Hochhaus, Andreas; Gruhn, Bernd; Ernst, Thomas

    2016-07-01

    Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and young adults. The polycomb repressive complex 2 (PRC2) has been identified as one of the most frequently mutated epigenetic protein complexes in hematologic cancers. PRC2 acts as an epigenetic repressor through histone H3 lysine 27 trimethylation (H3K27me3), catalyzed by the histone methyltransferase enhancer of zeste homolog 2 protein (EZH2). To study the prevalence and clinical impact of PRC2 aberrations in an unselected childhood ALL cohort (n = 152), we performed PRC2 mutational screenings by Sanger sequencing and promoter methylation analyses by quantitative pyrosequencing for the three PRC2 core component genes EZH2, suppressor of zeste 12 (SUZ12), and embryonic ectoderm development (EED). Targeted deep next-generation sequencing of 30 frequently mutated genes in leukemia was performed to search for cooperating mutations in patients harboring PRC2 aberrations. Finally, the functional consequence of EZH2 promoter hypermethylation on H3K27me3 was studied by Western blot analyses of primary cells. Loss-of-function EZH2 mutations were detected in 2/152 (1.3 %) patients with common-ALL and early T-cell precursor (ETP)-ALL, respectively. In one patient, targeted deep sequencing identified cooperating mutations in ASXL1 and TET2. EZH2 promoter hypermethylation was found in one patient with ETP-ALL which led to reduced H3K27me3. In comparison with healthy children, the EZH2 promoter was significantly higher methylated in T-ALL patients. No mutations or promoter methylation changes were identified for SUZ12 or EED genes, respectively. Although PRC2 aberrations seem to be rare in childhood ALL, our findings indicate that EZH2 aberrations might contribute to the disease in specific cases. Hereby, EZH2 promoter hypermethylation might have functionally similar consequences as loss-of-function mutations.

  19. Delayed-type hypersensitivity in response to L-asparaginase in a case of acute lymphoblastic leukemia.

    Science.gov (United States)

    Narazaki, Hidehiko; Kaizu, Kiyohiko; Miyatake, Chiharu; Koizumi, Shinya; Asano, Takeshi; Fujino, Osamu

    2012-01-01

    L-asparaginase (L-Asp) is an important reagent for acute lymphoblastic leukemia because asparagine is required for the malignant growth of tumor cells, especially lymphoblastic leukemia cells. An allergic response to L-Asp is not unusual because L-Asp is derived from Escherichia coli and is often recognized as a foreign protein. The hypersensitivity induced by L-Asp is of the immediate type in most cases. We report on a 5-year-old girl who was hospitalized for precursor T-cell lymphoblastic leukemia. She was treated according to a Tokyo Children's Cancer Study Group protocol (TCCSG ALL L09-1603 HEX/BFM). During the intensification phase, blisters with erythema developed on the arm proximal to the catheter insertion site owing to a delayed-type hypersensitivity reaction caused by intravenous L-Asp administration. She was treated with additional methylprednisolone, tapered dexamethasone, and an antihistamine for the allergic reaction. No asparaginases other than E. coli L-Asp have been approved for use in Japan. Other asparaginases, such as polyethylene glycol L-Asp and Erwinia L-Asp should be quickly approved for use as alternative chemotherapy reagents in Japan.

  20. Small molecule inhibition of CBP/catenin interactions eliminates drug resistant clones in acute lymphoblastic leukemia

    Science.gov (United States)

    Gang, Eun Ji; Hsieh, Yao-Te; Pham, Jennifer; Zhao, Yi; Nguyen, Cu; Huantes, Sandra; Park, Eugene; Naing, Khatija; Klemm, Lars; Swaminathan, Srividya; Conway, Edward M.; Pelus, Louis M.; Crispino, John; Mullighan, Charles; McMillan, Michael; Müschen, Markus; Kahn, Michael; Kim, Yong-Mi

    2014-01-01

    Drug resistance in acute lymphoblastic leukemia (ALL) remains a major problem warranting new treatment strategies. Wnt/catenin signaling is critical for the self-renewal of normal hematopoietic progenitor cells. Deregulated Wnt signaling is evident in chronic and acute myeloid leukemia, however little is known about ALL. Differential interaction of catenin with either the Kat3 coactivator CREBBP (CBP) or the highly homologous EP300 (p300) is critical to determine divergent cellular responses and provides a rationale for the regulation of both proliferation and differentiation by the Wnt signaling pathway. Usage of the coactivator CBP by catenin leads to transcriptional activation of cassettes of genes that are involved in maintenance of progenitor cell self-renewal. However, the use of the coactivator p300, leads to activation of genes involved in the initiation of differentiation. ICG-001 is a novel small molecule modulator of Wnt/catenin signaling, which specifically binds to the N-terminus of CBP and not p300, within amino acids 1–110, thereby disrupting the interaction between CBP and catenin. Here, we report that selective disruption of the CBP/β- and γ-catenin interactions using ICG-001 leads to differentiation of pre-B ALL cells and loss of self-renewal capacity. Survivin, an inhibitor-of-apoptosis protein, was also downregulated in primary ALL after treatment with ICG-001. Using ChIP assay, we demonstrate occupancy by CBP of the survivin promoter, which is decreased by ICG-001 in primary ALL. CBP-mutations have been recently identified in a significant percentage of ALL patients, however, almost all of the identified mutations reported occur C-terminal to the binding site for ICG-001. Importantly, ICG-001, regardless of CBP mutational status and chromosomal aberration, leads to eradication of drug-resistant primary leukemia in combination with conventional therapy in vitro and significantly prolongs the survival of NOD/SCID mice engrafted with primary

  1. Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation

    DEFF Research Database (Denmark)

    Nicolini, Franck E; Mauro, Michael J; Martinelli, Giovanni

    2009-01-01

    The BCR-ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP......), or blastic-phase (BP) and Philadelphia chromosome-positive (Ph)(+) acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation...

  2. High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols

    DEFF Research Database (Denmark)

    Paulsson, Kajsa Maria; Forestier, Erik; Andersen, Mette K

    2013-01-01

    Between 1992 and 2008, 713 high hyperdiploid acute lymphoblastic leukemias in children aged 1-15 years were diagnosed and treated according to the Nordic Society for Pediatric Hematology and Oncology acute lymphoblastic leukemia 1992/2000 protocols. Twenty (2.8%) harbored t(1;19), t(9;22), der(11q...

  3. Home paint exposures and risk of childhood acute lymphoblastic leukemia: findings from the Childhood Leukemia International Consortium.

    Science.gov (United States)

    Bailey, Helen D; Metayer, Catherine; Milne, Elizabeth; Petridou, Eleni Th; Infante-Rivard, Claire; Spector, Logan G; Clavel, Jacqueline; Dockerty, John D; Zhang, Luoping; Armstrong, Bruce K; Rudant, Jérémie; Fritschi, Lin; Amigou, Alicia; Hatzipantelis, Emmanuel; Kang, Alice Y; Stiakaki, Eftichia; Schüz, Joachim

    2015-09-01

    It has been suggested that home paint exposure increases the risk of childhood acute lymphoblastic leukemia (ALL). We obtained individual level data from eight case-control studies participating in the Childhood Leukemia International Consortium. All studies had home paint exposure data (sometimes including lacquers and varnishes) for the pregnancy period with additional data for the 1-3-month period before conception in five, the year before conception in two, and the period after birth in four studies, respectively. Cytogenetic subtype data were available for some studies. Data were harmonized to a compatible format. Pooled analyses of individual data were undertaken using unconditional logistic regression. Based on 3,002 cases and 3,836 controls, the pooled odds ratio (OR) for home paint exposure in the 1-3 months before conception and risk of ALL was 1.54 [95% confidence interval (CI) 1.28, 1.85], while based on 1,160 cases and 1,641 controls for exposure in the year before conception, it was 1.00 (95% CI 0.86, 1.17). For exposure during pregnancy, using 4,382 cases and 5,747 controls, the pooled OR was 1.14 (95% CI 1.04, 1.25), and for exposure after birth, the OR was 1.22 (95% CI 1.07, 1.39), based on data from 1,962 cases and 2,973 controls. The risk was greater for certain cytogenetic subtypes and if someone other than the parents did the painting. Home paint exposure shortly before conception, during pregnancy, and/or after birth appeared to increase the risk of childhood ALL. It may be prudent to limit exposure during these periods.

  4. AZD1775 sensitizes T cell acute lymphoblastic leukemia cells to cytarabine by promoting apoptosis over DNA repair.

    Science.gov (United States)

    Ford, James B; Baturin, Dmitry; Burleson, Tamara M; Van Linden, Annemie A; Kim, Yong-Mi; Porter, Christopher C

    2015-09-29

    While some children with acute lymphoblastic leukemia (ALL) have excellent prognoses, the prognosis for adults and children with T cell ALL is more guarded. Treatment for T-ALL is heavily dependent upon antimetabolite chemotherapeutics, including cytarabine. Targeted inhibition of WEE1 with AZD1775 has emerged as a strategy to sensitize cancer cells to cytarabine and other chemotherapeutics. We sought to determine if this strategy would be effective for T-ALL with clinically relevant anti-leukemia agents. We found that AZD1775 sensitizes T-ALL cells to several traditional anti-leukemia agents, acting synergistically with cytarabine by enhancing DNA damage and apoptosis. In addition to increased phosphorylation of H2AX at serine 139 (γH2AX), AZD1775 led to increased phosphorylation of H2AX at tyrosine 142, a signaling event associated with promotion of apoptosis over DNA repair. In a xenograft model of T-ALL, the addition of AZD1775 to cytarabine slowed leukemia progression and prolonged survival. Inhibition of WEE1 with AZD1775 sensitizes T-ALL to several anti-leukemia agents, particularly cytarabine and that mechanistically, AZD1775 promotes apoptosis over DNA repair in cells treated with cytarabine. These data support the development of clinical trials including AZD1775 in combination with conventional chemotherapy for acute leukemia.

  5. 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.

  6. 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.

  7. THE ANALYSIS OF THE RESULTS OF ACUTE LYMPHOBLAST LEUKEMIA TREATMENT IN CHILDREN USING A MODIFIED PROTOCOL COALL 92 IN ST. PETERSBURG

    Directory of Open Access Journals (Sweden)

    E.G. Boichenko

    2006-01-01

    Full Text Available The article presents the results of the treatment of children with acute lymphoblast leukemia (all according to the coall 92 program in St.-Petersburg from 01.01.1999 to 01.01.2005. 160 primary all patients, aged 4 months to 17 years 4 months were included in the study. International criteria were used to diagnose acute lymphoblast leukemia. A 2 years course of treatment in both risk groups included a 5,5–8 months phase of intensive chemotherapy followed by maintenance therapy. 6 years after the protocol introduction in the common group of patients the following survival rate indices were obtained: the 6 years uneventful survival rate was 63 ± 4,6%, the 6 years relapses free survival rate was 69 ± 4,7%, the 6 years general survival rate was 79 ± 3,7%.Key words: acute lymphoblast leukemia, children, intensive chemotherapy.

  8. Intrachromosomal amplification of chromosome 21 (iAMP21 detected by ETV6/RUNX1 FISH screening in childhood acute lymphoblastic leukemia: a case report

    Directory of Open Access Journals (Sweden)

    Daniela Ribeiro Ney Garcia

    2013-01-01

    Full Text Available Chromosome abnormalities that usually define high-risk acute lymphoblastic leukemia are the t(9;22/ breakpoint cluster region protein-Abelson murine leukemia viral oncogene homolog 1, hypodiploid with < 44 chromosomes and 11q23/ myeloid/lymphoid leukemia gene rearrangements. The spectrum of acute lymphoblastic leukemia genetic abnormalities is nevertheless rapidly expanding. Therefore, newly described chromosomal aberrations are likely to have an impact on clinical care in the near future. Recently, the rare intrachromosomal amplification of chromosome 21 started to be considered a high-risk chromosomal abnormality. It occurs in approximately 2-5% of pediatric patients with B-cell precursor acute lymphoblastic leukemia. This abnormality is associated with a poor outcome. Hence, an accurate detection of this abnormality is expected to become very important in the choice of appropriate therapy. In this work the clinical and molecular cytogenetic evaluation by fluorescence in situ hybridization of a child with B-cell precursor acute lymphoblastic leukemia presenting the rare intrachromosomal amplification of chromosome 21 is described.

  9. Intrachromosomal amplification of chromosome 21 (iAMP21) detected by ETV6/RUNX1 FISH screening in childhood acute lymphoblastic leukemia: a case report

    Science.gov (United States)

    Garcia, Daniela Ribeiro Ney; Arancibia, Alejandro Mauricio; Ribeiro, Raul C.; Land, Marcelo Gerardin Poirot; Silva, Maria Luiza Macedo

    2013-01-01

    Chromosome abnormalities that usually define high-risk acute lymphoblastic leukemia are the t(9;22)/ breakpoint cluster region protein-Abelson murine leukemia viral oncogene homolog 1, hypodiploid with < 44 chromosomes and 11q23/ myeloid/lymphoid leukemia gene rearrangements. The spectrum of acute lymphoblastic leukemia genetic abnormalities is nevertheless rapidly expanding. Therefore, newly described chromosomal aberrations are likely to have an impact on clinical care in the near future. Recently, the rare intrachromosomal amplification of chromosome 21 started to be considered a high-risk chromosomal abnormality. It occurs in approximately 2-5% of pediatric patients with B-cell precursor acute lymphoblastic leukemia. This abnormality is associated with a poor outcome. Hence, an accurate detection of this abnormality is expected to become very important in the choice of appropriate therapy. In this work the clinical and molecular cytogenetic evaluation by fluorescence in situ hybridization of a child with B-cell precursor acute lymphoblastic leukemia presenting the rare intrachromosomal amplification of chromosome 21 is described. PMID:24255623

  10. Discovery and identification of potential biomarkers of pediatric Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Cui Ziyou

    2009-03-01

    Full Text Available Abstract Background Acute lymphoblastic leukemia (ALL is a common form of cancer in children. Currently, bone marrow biopsy is used for diagnosis. Noninvasive biomarkers for the early diagnosis of pediatric ALL are urgently needed. The aim of this study was to discover potential protein biomarkers for pediatric ALL. Methods Ninety-four pediatric ALL patients and 84 controls were randomly divided into a "training" set (45 ALL patients, 34 healthy controls and a test set (49 ALL patients, 30 healthy controls and 30 pediatric acute myeloid leukemia (AML patients. Serum proteomic profiles were measured using surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy (SELDI-TOF-MS. A classification model was established by Biomarker Pattern Software (BPS. Candidate protein biomarkers were purified by HPLC, identified by LC-MS/MS and validated using ProteinChip immunoassays. Results A total of 7 protein peaks (9290 m/z, 7769 m/z, 15110 m/z, 7564 m/z, 4469 m/z, 8937 m/z, 8137 m/z were found with differential expression levels in the sera of pediatric ALL patients and controls using SELDI-TOF-MS and then analyzed by BPS to construct a classification model in the "training" set. The sensitivity and specificity of the model were found to be 91.8%, and 90.0%, respectively, in the test set. Two candidate protein peaks (7769 and 9290 m/z were found to be down-regulated in ALL patients, where these were identified as platelet factor 4 (PF4 and pro-platelet basic protein precursor (PBP. Two other candidate protein peaks (8137 and 8937 m/z were found up-regulated in the sera of ALL patients, and these were identified as fragments of the complement component 3a (C3a. Conclusion Platelet factor (PF4, connective tissue activating peptide III (CTAP-III and two fragments of C3a may be potential protein biomarkers of pediatric ALL and used to distinguish pediatric ALL patients from healthy controls and pediatric AML patients. Further studies with

  11. Alteration in Bone Mineral Metabolism in Children with Acute Lymphoblastic Leukemia (ALL: A Review

    Directory of Open Access Journals (Sweden)

    Chowdhury Yakub Jamal

    2009-11-01

    Full Text Available In recent years there has been a significant increase in event free survival (EFS and overall survival in children with cancer. As survival rates for childhood cancer have radically improved, late effects associated with the successful but highly intensive chemotherapy and/or radiotherapy have dramatically increased. Many possible late effects of cancer treatment are recognized in pediatric cancer patients as infertility, endocrine deficiency, renal failure, pulmonary and cardiac toxicity, obesity and osteopenia/osteoporosis. Decreased bone mineral density (BMD and bone metabolism disturbances have been recognized and reported in literature. Osteopenia/osteoporosis skeletal abnormalities, osteonecrosis and pathological fractures are known to occur frequently in childhood acute lymphoblastic leukemia (ALL at diagnosis, during and after treatment with chemotherapy. Various studies have revealed different metabolic alterations related to ALL. Some suggestions have been made about their relationship with the disease process. Various metabolic abnormalities may be encountered in the newly diagnosed ALL patients. It includes decreased and increased serum levels of calcium and phosphate. Hypercalcemia may result from leukemic infiltrations of bone and release of parathormone like substance from lymphoblast. Elevated serum phosphate can occur as a result of leukemic cell lysis and may induce hypocalcemia. It has been postulated by other authors that leukemic cells may directly infiltrate bone and produce parathroid hormone related peptides, prostaglandin E and osteoblast inhibiting factors. Hypomagnesemia, hypocalcaemia and hypothyroidisum have been demonstrated in patients with ALL. Some patients may have poor nutrition and decreased physical activities during treatment. However postulations have also been made that chemotherapy may play a role in creating metabolic alterations in children with ALL. Corticosteroid, methotraxate and cranial irradiations

  12. Senescent stromal cell-induced divergence and therapeutic resistance in T cell acute lymphoblastic leukemia/lymphoma.

    Science.gov (United States)

    Habiel, David M; Krepostman, Nicolas; Lilly, Michael; Cavassani, Karen; Coelho, Ana Lucia; Shibata, Takehiko; Elenitoba-Johnson, Kojo; Hogaboam, Cory M

    2016-12-13

    T cell Acute Lymphoblastic Leukemia/Lymphoma (T-ALL/LBL) is a precursor T cell leukemia/lymphoma that represents approximately 15% of all childhood and 25% of adult acute lymphoblastic leukemia. Although a high cure rate is observed in children, therapy resistance is often observed in adults and mechanisms leading to this resistance remain elusive. Utilizing public gene expression datasets, a fibrotic signature was detected in T-LBL but not T-ALL biopsies. Further, using a T-ALL cell line, CCRF-CEM (CEM) cells, we show that CEM cells induce pulmonary remodeling in immunocompromised mice, suggesting potential interaction between these cells and lung fibroblasts. Co-culture studies suggested that fibroblasts-induced phenotypic and genotypic divergence in co-cultured CEM cells leading to diminished therapeutic responses in vitro. Senescent rather than proliferating stromal cells induced these effects in CEM cells, due, in part, to the enhanced production of oxidative radicals and exosomes containing miRNAs targeting BRCA1 and components of the Mismatch Repair pathway (MMR). Collectively, our studies demonstrate that there may be bidirectional interaction between leukemic cells and stroma, where leukemic cells induce stromal development in vivo and senescent stromal cells generates genomic alterations in the leukemic cells rendering them therapeutic resistant. Thus, targeting senescent stroma might prove beneficial in T-ALL/LBL patients.

  13. Treatment of relapsed precursor-B acute lymphoblastic leukemia with intensive chemotherapy: POG (Pediatric Oncology Group) study 9411 (SIMAL 9).

    Science.gov (United States)

    Kelly, Michael E; Lu, Xiaomin; Devidas, Meenakshi; Camitta, Bruce; Abshire, Thomas; Bernstein, Mark L; Billett, Amy; Homans, Alan; Sandler, Eric; Buchanan, George

    2013-10-01

    Pediatric patients who experience a bone marrow relapse of precursor-B acute lymphoblastic leukemia are cured <50% of the time. This study was designed to determine if intensification of therapies with known activity in this disease would improve the cure rates for patients with relapsed acute lymphoblastic leukemia. Patients were treated with intensive asparaginase during induction followed by repeated cycles of ifosfamide/etoposide and cytarabine/idarubicin. Patients with well-matched related donors were encouraged to undergo hematopoietic stem cell transplant as consolidation. The results of this study demonstrate no significant difference in disease-free survival in patients who received chemotherapy alone (45%) or chemotherapy followed by allogeneic stem cell transplant (50%). Furthermore, results from this study show no significant difference in event-free survival (39.9%±6.2%) or overall survival (41.6%±6.1%) at 8 years when compared with previous studies using less intensive regimens. Our results suggest that alternative therapies are needed to improve cure rates for pediatric patients with relapsed leukemia.

  14. Tyrosine kinase inhibitors improve long-term outcome of allogeneic hematopoietic stem cell transplantation for adult patients with philadelphia chromosome positive acute lymphoblastic leukemia

    NARCIS (Netherlands)

    E. Brissot (Eolia); M. Labopin (Myriam); M.M. Beckers (Marielle M.); G. Socié (Gerard); A. Rambaldi (Alessandro); L. Volin (Liisa); J. Finke (Jürgen); S. Lenhoff (S.); N. Kröger; G.J. Ossenkoppele (Gert); C.F. Craddock (Charles); I. Yakoub-Agha (Ibrahim); G. Gürman (Günhan); N.H. Russell (Nigel H.); M. Aljurf (Mahmoud); M. Potter (M.); A. Nagler (Arnon); O.G. Ottmann; J.J. Cornelissen (Jan); J. Esteve (Jordi); M. Mohty (Mohamad)

    2015-01-01

    textabstractThis study aimed to determine the impact of tyrosine kinase inhibitors given pre- and post-allogeneic stem cell transplantation on long-term outcome of patients allografted for Philadelphia chromosome-positive acute lymphoblastic leukemia. This retrospective analysis from the EBMT Acute

  15. Analysis of KRAS and NRAS Gene Mutations in Arab Asian Children With Acute Leukemia: High Frequency of RAS Mutations in Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Al-Kzayer, Lika'a Fasih Y; Sakashita, Kazuo; Al-Jadiry, Mazin Faisal; Al-Hadad, Salma Abbas; Ghali, Hasanein Habeeb; Uyen, Le T N; Liu, Tingting; Matsuda, Kazuyuki; Abdulkadhim, Jaafar M H; Al-Shujairi, Tariq Abadi; Matti, Zead Ismael I K; Sughayer, Maher A; Rihani, Rawad; Madanat, Faris F; Inoshita, Toshi; Kamata, Minoru; Koike, Kenichi

    2015-12-01

    KRAS and NRAS gene mutations are frequently observed in childhood leukemia. The objective of this study was to determine the frequency of RAS mutations and the association between RAS mutations and other genetic aberrations in Arab Asian children with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Diagnostic samples of 485 patients (RAS mutations were detected in 86/318 (27%) of ALL cases and 35/167 (21%) of AML cases. The frequency of NRAS mutation was similar to that of KRAS mutation in ALL. Two RAS mutations were detected in nine patients. Among 264 Iraqi patients with ALL, RAS mutation was significantly associated with lower initial white blood cell count. Of 57 patients with chimeric transcripts, only two patients with either TEL-AML1 or E2A-PBX1 had KRAS mutation. The frequency of NRAS mutation was four times higher than that of KRAS mutation in AML. FAB-M4 and M5 subsets were associated with RAS mutation. Among 134 Iraqi patients with AML, 18 patients had RAS mutations and other genetic aberrations. In particular, 9 of 25 (36%) with MLL-rearrangement had RAS mutations. The prevalence of oncogenic RAS mutations was higher among Arab Asian children than in other countries. RAS mutations in AML were found to coexist with other genetic aberrations, particularly MLL rearrangement. © 2015 Wiley Periodicals, Inc.

  16. ASSOCIATION OF 1800 CGY CRANIAL IRRADIATION WITH INTELLECTUAL FUNCTION IN CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIA

    NARCIS (Netherlands)

    JANKOVIC, M; BROUWERS, P; VALSECCHI, MG; VANVELDHUIZEN, A; KAMPHUIS, R; KINGMA, A; MOR, W; VANDONGENMELMAN, J; FERRONATO, L; MANCINI, MA; SPINETTA, JJ; MASERA, G

    1994-01-01

    Cranial radiation therapy in childhood acute lymphoblastic leukaemia has been associated with adverse neuropsychological effects, such as low intelligence. However, records show that these associations usually occur when the dose of radiation used is 2400 cGy. We investigated whether a lower dose of

  17. 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......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...

  18. Precise quantification of minimal residual disease at day 29 allows identification of children with acute lymphoblastic leukemia and an excellent outcome

    DEFF Research Database (Denmark)

    Nyvold, Charlotte; Madsen, Hans O; Ryder, Lars P

    2002-01-01

    The postinduction level of minimal residual disease (MRD) was quantified with a competitive polymerase chain reaction (PCR) technique in 104 children with acute lymphoblastic leukemia (ALL) diagnosed between June 1993 and January 1998 and followed for a median of 4.2 years. A significant correlat......The postinduction level of minimal residual disease (MRD) was quantified with a competitive polymerase chain reaction (PCR) technique in 104 children with acute lymphoblastic leukemia (ALL) diagnosed between June 1993 and January 1998 and followed for a median of 4.2 years. A significant...

  19. A successful treatment of hypercalcemia with zoledronic acid in a 15-year-old boy with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Hye-Jin Park

    2016-06-01

    Full Text Available Severe hypercalcemia in children is a rare medical emergency. We present a case of a 15-year-old boy with hypercalcemia (total calcium level, 14.2 mg/dL with a normal complete blood count, no circulating blasts in the peripheral blood film, and no other signs of acute lymphoblastic leukemia (ALL, including no signs of lymphadenopathy or hepatosplenomegaly. The hypercalcemia was successfully treated with zoledronic acid. As hypercalcemia can be the only presenting symptom of ALL in children, the diagnosis is often delayed. In children presenting with hypercalcemia, malignancies must be considered in the differential diagnosis.

  20. CT and MR imaging findings of appendiceal and hepatic mucormycosis in a patient with acute T-lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia | Office of Cancer Genomics

    Science.gov (United States)

    Genetic alterations that activate NOTCH1 signaling and T cell transcription factors, coupled with inactivation of the INK4/ARF tumor suppressors, are hallmarks of T-lineage acute lymphoblastic leukemia (T-ALL), but detailed genome-wide sequencing of large T-ALL cohorts has not been carried out. Using integrated genomic analysis of 264 T-ALL cases, we identified 106 putative driver genes, half of which had not previously been described in childhood T-ALL (for example, CCND3, CTCF, MYB, SMARCA4, ZFP36L2 and MYCN).

  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. Socioeconomic status and event free survival in pediatric acute lymphoblastic leukemia: a population-based cohort study.

    Science.gov (United States)

    Gupta, Sumit; Sutradhar, Rinku; Guttmann, Astrid; Sung, Lillian; Pole, Jason D

    2014-12-01

    The impact of socioeconomic status (SES) upon childhood cancer outcomes has not been extensively examined. Our objective was to determine the association between SES and event-free survival (EFS) among children with acute lymphoblastic leukemia (ALL) diagnosed in Ontario, Canada from 1995-2011 (N=1541) using Cox proportional hazards. Neither neighborhood-level median income quintile, distance from tertiary center, or rural residence significantly predicted EFS in the context of a universal healthcare system. Immigrant children experienced significantly superior EFS; confounding by ethnicity could not be ruled out. Confirmatory studies using additional individual-level SES variables are warranted. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. DNA methylation for subtype classification and prediction of treatment outcome in patients with childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Milani, Lili; Lundmark, Anders; Kiialainen, Anna

    2010-01-01

    Despite improvements in the prognosis of childhood acute lymphoblastic leukemia (ALL), subgroups of patients would benefit from alternative treatment approaches. Our aim was to identify genes with DNA methylation profiles that could identify such groups. We determined the methylation levels of 1320...... CpG sites in regulatory regions of 416 genes in cells from 401 children diagnosed with ALL. Hierarchical clustering of 300 CpG sites distinguished between T-lineage ALL and B-cell precursor (BCP) ALL and between the main cytogenetic subtypes of BCP ALL. It also stratified patients with high...

  5. Whole-genome DNA methylation characteristics in pediatric precursor B cell acute lymphoblastic leukemia (BCP ALL.

    Directory of Open Access Journals (Sweden)

    Radosław Chaber

    Full Text Available In addition to genetic alterations, epigenetic abnormalities have been shown to underlie the pathogenesis of acute lymphoblastic leukemia (ALL-the most common pediatric cancer. The purpose of this study was to characterize the whole genome DNA methylation profile in children with precursor B-cell ALL (BCP ALL and to compare this profile with methylation observed in normal bone marrow samples. Additional efforts were made to correlate the observed methylation patterns with selected clinical features. We assessed DNA methylation from bone marrow samples obtained from 38 children with BCP ALL at the time of diagnosis along with 4 samples of normal bone marrow cells as controls using Infinium MethylationEPIC BeadChip Array. Patients were diagnosed and stratified into prognosis groups according to the BFM ALL IC 2009 protocol. The analysis of differentially methylated sites across the genome as well as promoter methylation profiles allowed clear separation of the leukemic and control samples into two clusters. 86.6% of the promoter-associated differentially methylated sites were hypermethylated in BCP ALL. Seven sites were found to correlate with the BFM ALL IC 2009 high risk group. Amongst these, one was located within the gene body of the MBP gene and another was within the promoter region- PSMF1 gene. Differentially methylated sites that were significantly related with subsets of patients with ETV6-RUNX1 fusion and hyperdiploidy. The analyzed translocations and change of genes' sequence context does not affect methylation and methylation seems not to be a mechanism for the regulation of expression of the resulting fusion genes.

  6. Pharmacokinetics of two 6-mercaptopurine liquid formulations in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Tolbert, Jaszianne A; Bai, Shasha; Abdel-Rahman, Susan M; August, Keith J; Weir, Scott J; Kearns, Gregory L; Neville, Kathleen A

    2017-08-01

    A liquid formulation of 6-mercaptopurine (6-MP) was recently approved by the Food and Drug Administration (Purixan®) based on bioavailability (BA) data from healthy adults. We examined the pharmacokinetics (PK) and BA of 6-MP in children with acute lymphoblastic leukemia (ALL) comparing a marketed tablet, two extemporaneously prepared liquid formulations, and data from the approved liquid formulation. Twenty-two children (6-17 years) participated in a randomized two-way, crossover study of two cohorts. Group 1 (n = 11; five males) received a 5 mg/ml liquid formulation and the marketed 50 mg 6-MP tablet on separate occasions, and Group 2 (n = 11; five males) received a 50 mg/ml liquid formulation and the marketed tablet. The usual prescribed 6-MP dose (25-115 mg/m 2 ) was given after an 8-hr fast. Serial blood samples were collected over 8 hr postdose. Plasma 6-MP concentrations were determined using a good laboratory practice (GLP)-validated liquid chromatography-tandem mass spectrometry method. PK parameters were calculated using noncompartmental analysis and compared within and between cohorts, and thiopurine methyltransferase (TPMT) genotype was analyzed. No patient had a TPMT genotype reflective of a poor metabolizer phenotype. Comparison of PK parameters between 5 and 50 mg/ml treatments revealed significant differences (P <0.05) in AUC N (where AUC is area under the curve), C maxN , and T max . Comparisons within each group revealed significant differences in AUC 0-∞ and T max in the 5 mg/ml group. Pharmacokinetic profiles of 6-MP established in healthy adults with the approved liquid formulation may not reflect the PK profile in children with ALL. Formulation-specific differences in PK may significantly impact the dose-exposure profile in these children and must be considered. © 2017 Wiley Periodicals, Inc.

  7. Health-Related Quality of Life Among Children with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Furlong, William; Rae, Charlene; Feeny, David; Gelber, Richard D; Laverdiere, Caroline; Michon, Bruno; Silverman, Lewis; Sallan, Stephen; Barr, Ronald

    2014-01-01

    BACKGROUND The objective was to quantify the health-related quality of life (HRQL) of children treated for acute lymphoblastic leukemia (ALL) and identify specific disabilities for remediation. PROCEDURE Two types of subjects were included: ALL patients 5 plus years old in a multi-center clinical trial; and general population control groups. Patients were assessed during all 4 major phases of active treatment and approximately 2 years after treatment. Health status and HRQL were measured using HEALTH UTILITIES INDEX® (HUI®) Mark 2 (HUI2) and Mark 3 (HUI3). HRQL scores were used to calculate quality-adjusted life years (QALYs). Excess disability rates identified attributes for remediation. RESULTS HUI assessments (n=749) were collected during the 5 phases. Mean HRQL increased from induction through the post-treatment phase (p<0.001). There were no significant demographic or treatment effects on HRQL, except for type of asparaginase during continuation therapy (p=0.005 for HUI2 and p=0.007 for HUI3). Differences in mean HRQL scores between patients and controls were important (p<0.001) during the active treatment phases but not during the post-treatment phase. Relative to controls, patients lost approximately 0.2 QALYs during active treatment. Disability was evident in mobility/ambulation, emotion, self-care and pain, and declined over time. CONCLUSIONS Patients with ALL experienced important but declining deficits in HRQL during active treatment phases: equivalent to losing approximately 2 months of life in perfect health. HRQL within the 2-years post-treatment phase was similar to controls. The policy challenge is to develop new treatment protocols producing fewer disabilities in mobility/ambulation, emotion, self-care, and pain without compromising survival. PMID:22294502

  8. Screening survivors of childhood acute lymphoblastic leukemia for obesity, metabolic syndrome, and insulin resistance.

    Science.gov (United States)

    Karakurt, Hasan; Sarper, Nazan; Kılıç, Suar Çakı; Gelen, Sema Aylan; Zengin, Emine

    2012-09-01

    Acute lymphoblastic leukemia (ALL) survivors were screened for risk factors of cardiovascular disease. Forty-four ALL survivors in first remission were enrolled. Twenty-six also received 12-18 Gy cranial radiotherapy (RT). Patients' body mass indexes (BMIs) at dignosis and during the study were compared. Metabolic syndrome (MS) evaluation was performed in patients, parents, and siblings older than 6 years. Homeostasis Model Assessment (HOMA) index of the survivors was also calculated. In survivors with impaired fasting glucose levels, oral glucose tolerance test (OGTT) was performed. Thyroid functions and IGF-1 and/or IGFBP-3 levels of the survivors who received cranial RT were evaluated. Median age of the survivors was 11.5 years (6-23). At diagnosis, mean BMI percentile was 46.7 (3-95) and mean z-score was -0.09 ± 1.14; during the study, these values rose to 71.1 ± 25.6 (3-100) and 0.8 ± 0.94, respectively (P obese at diagnosis and during the study, respectively (P = .005). Survivors had significantly higher BMI percentile and BMI z-score compared to their siblings (P = .006 and P = .011, respectively). The study group was small and we could not show a correlation of the patients' obesity with RT, thyroid functions, IGF-1, and IGFBP-3 levels. In three survivors (6.8%), there was MS. Maternal and paternal MS was not found as a risk factor for MS of the survivors (P = .1, P = .5, respectively). The HOMA index revealed insulin resistance (IR) in 12 (27.2%) of the survivors, whereas OGTT revealed abnormal glucose regulation and/or IR in four. As a conclusion, ALL survivors have high risk for obesity and MS.

  9. Regulation of cancer stem cell properties by CD9 in human B-acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Hiroto [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Wilson Xu, C. [Drug Development Program, Nevada Cancer Institute, Las Vegas, NV (United States); Naito, Motohiko [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Nishida, Hiroko [Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo (Japan); Okamoto, Toshihiro; Ghani, Farhana Ishrat; Iwata, Satoshi [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Inukai, Takeshi; Sugita, Kanji [Department of Pediatrics, School of Medicine, University of Yamanashi, Yamanashi (Japan); Morimoto, Chikao, E-mail: morimoto@ims.u-tokyo.ac.jp [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Drug Development Program, Nevada Cancer Institute, Las Vegas, NV (United States)

    2011-05-27

    Highlights: {yields} We performed more detailed analysis of CD9 function for CSC properties in B-ALL. {yields} Leukemogenic fusion/Src family proteins were markedly regulated in the CD9{sup +} cells. {yields} Proliferation of B-ALL cells was inhibited by anti-CD9 monoclonal antibody. {yields} Knockdown of CD9 by RNAi remarkably reduced the leukemogenic potential. {yields} CD9-knockdown affected the expression and phosphorylation of Src family and USP22. -- Abstract: Although the prognosis of acute lymphoblastic leukemia (ALL) has improved considerably in recent years, some of the cases still exhibit therapy-resistant. We have previously reported that CD9 was expressed heterogeneously in B-ALL cell lines and CD9{sup +} cells exhibited an asymmetric cell division with greater tumorigenic potential than CD9{sup -} cells. CD9{sup +} cells were also serially transplantable in immunodeficient mice, indicating that CD9{sup +} cell possess self-renewal capacity. In the current study, we performed more detailed analysis of CD9 function for the cancer stem cell (CSC) properties. In patient sample, CD9 was expressed in the most cases of B-ALL cells with significant correlation of CD34-expression. Gene expression analysis revealed that leukemogenic fusion proteins and Src family proteins were significantly regulated in the CD9{sup +} population. Moreover, CD9{sup +} cells exhibited drug-resistance, but proliferation of bulk cells was inhibited by anti-CD9 monoclonal antibody. Knockdown of CD9 remarkably reduced the leukemogenic potential. Furthermore, gene ablation of CD9 affected the expression and tyrosine-phosphorylation of Src family proteins and reduced the expression of histone-deubiquitinase USP22. Taken together, our results suggest that CD9 links to several signaling pathways and epigenetic modification for regulating the CSC properties of B-ALL.

  10. 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.

  11. Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia

    Science.gov (United States)

    Ellinghaus, E; Stanulla, M; Richter, G; Ellinghaus, D; te Kronnie, G; Cario, G; Cazzaniga, G; Horstmann, M; Panzer Grümayer, R; Cavé, H; Trka, J; Cinek, O; Teigler-Schlegel, A; ElSharawy, A; Häsler, R; Nebel, A; Meissner, B; Bartram, T; Lescai, F; Franceschi, C; Giordan, M; Nürnberg, P; Heinzow, B; Zimmermann, M; Schreiber, S; Schrappe, M; Franke, A

    2012-01-01

    Acute lymphoblastic leukemia (ALL) is a malignant disease of the white blood cells. The etiology of ALL is believed to be multifactorial and likely to involve an interplay of environmental and genetic variables. We performed a genome-wide association study of 355 750 single-nucleotide polymorphisms (SNPs) in 474 controls and 419 childhood ALL cases characterized by a t(12;21)(p13;q22) — the most common chromosomal translocation observed in childhood ALL — which leads to an ETV6–RUNX1 gene fusion. The eight most strongly associated SNPs were followed-up in 951 ETV6-RUNX1-positive cases and 3061 controls from Germany/Austria and Italy, respectively. We identified a novel, genome-wide significant risk locus at 3q28 (TP63, rs17505102, PCMH=8.94 × 10−9, OR=0.65). The separate analysis of the combined German/Austrian sample only, revealed additional genome-wide significant associations at 11q11 (OR8U8, rs1945213, P=9.14 × 10−11, OR=0.69) and 8p21.3 (near INTS10, rs920590, P=6.12 × 10−9, OR=1.36). These associations and another association at 11p11.2 (PTPRJ, rs3942852, P=4.95 × 10−7, OR=0.72) remained significant in the German/Austrian replication panel after correction for multiple testing. Our findings demonstrate that germline genetic variation can specifically contribute to the risk of ETV6–RUNX1-positive childhood ALL. The identification of TP63 and PTPRJ as susceptibility genes emphasize the role of the TP53 gene family and the importance of proteins regulating cellular processes in connection with tumorigenesis. PMID:22076464

  12. Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia: Clinical Facts and Fiction

    Science.gov (United States)

    Nielsen, Stine N.; Frandsen, Thomas L.; Nersting, Jacob

    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 dosing. Because of significant interindividual and intraindividual variations in drug disposition and pharmacodynamics, vigorous dose adjustments are needed to obtain a target degree of myelosuppression. As the normal white blood cell counts vary by patients’ ages and ethnicity, and also within age groups, identical white blood cell levels for 2 patients may not reflect the same treatment intensity. Measurements of intracellular levels of cytotoxic metabolites of 6MP and MTX can identify nonadherent patients, but therapeutic target levels remains to be established. A rise in serum aminotransferase levels during maintenance therapy is common and often related to high levels of methylated 6MP metabolites. However, except for episodes of hypoglycemia, serious liver dysfunction is rare, the risk of permanent liver damage is low, and aminotransferase levels usually normalize within a few weeks after discontinuation of therapy. 6MP and MTX dose increments should lead to either leukopenia or a rise in aminotransferases, and if neither is experienced, poor treatment adherence should be considered. The many genetic polymorphisms that determine 6MP and MTX disposition, efficacy, and toxicity have precluded implementation of pharmacogenomics into treatment, the sole exception being dramatic 6MP dose reductions in patients who are homozygous deficient for thiopurine methyltransferase, the enzyme that methylates 6MP and several of its metabolites. In conclusion, maintenance therapy is as important as the more intensive and toxic earlier treatment phases, and often more challenging. Ongoing research address the applicability of drug metabolite measurements for dose adjustments

  13. Hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Takaharu; Kato, Koji [Nagoya First Red Cross Hospital (Japan). Children' s Medical Center; Hanada, Ryoji [Saitama Children' s Medical Center, Iwatsuki (Japan)] [and others

    2002-07-01

    A multicenter comparative study was carried out to investigate the efficacy and safety of hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia. One hundred twenty three patients at a variety of remission stages were eligible for study participation. Eighty-nine were transplanted with allogeneic grafts and 34 patients with autologous grafts (23 cases with bone marrow and 11 cases with peripheral blood stem cells). Conditioning regimens used were as follows: melphalan and busulfan for 40 patients, melphalan, busulfan and TBI for 44 patients, other regimens for 39 patients. To accelerate engraftment G-CSF (lenograstim) was administered as a 1-hour or 24-hour drip infusion daily at 5 {mu}g/kg from day 5 until hematological recovery. The five year disease free survival (DFS) was 63% for 42 patients at CR1, 41% for 41 patients at CR2 and 33% for 40 patients at other stages. There was no significant difference in the DFS between allogeneic-transplantation and autologous-transplantation in all disease stages. In patients at remission stage for CR1 and CR2, the 5-year DFS by conditioning regimen was 63% for regimen with melphalan and busulfan, 54% for regimen with melphalan, busulfan and TBI and 54% for regimens with melphalan and TBI. There was no significant difference in the DFS between the groups. Serious complications such as renal failure were observed in 11%, veno-occlusive disease in 9%, and interstitial pneumonia in 9%. The most dominating cause of death was relapse in the disease (48% of deaths) which was most commonly observed in autologous transplantation. Contrary to that, treatment related toxic death was the most frequent cause of deaths in allogeneic-transplantation. (author)

  14. Tyrosine kinase fusion genes in pediatric BCR-ABL1-like acute lymphoblastic leukemia.

    Science.gov (United States)

    Boer, Judith M; Steeghs, Elisabeth M P; Marchante, João R M; Boeree, Aurélie; Beaudoin, James J; Beverloo, H Berna; Kuiper, Roland P; Escherich, Gabriele; van der Velden, Vincent H J; van der Schoot, C Ellen; de Groot-Kruseman, Hester A; Pieters, Rob; den Boer, Monique L

    2017-01-17

    Approximately 15% of pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by gene expression similar to that of BCR-ABL1-positive disease and unfavorable prognosis. This BCR-ABL1-like subtype shows a high frequency of B-cell development gene aberrations and tyrosine kinase-activating lesions. To evaluate the clinical significance of tyrosine kinase gene fusions in children with BCP-ALL, we studied the frequency of recently identified tyrosine kinase fusions, associated genetic features, and prognosis in a representative Dutch/German cohort. We identified 14 tyrosine kinase fusions among 77 BCR-ABL1-like cases (18%) and none among 76 non-BCR-ABL1-like B-other cases. Novel exon fusions were identified for RCSD1-ABL2 and TERF2-JAK2. JAK2 mutation was mutually exclusive with tyrosine kinase fusions and only occurred in cases with high CRLF2 expression. The non/late response rate and levels of minimal residual disease in the fusion-positive BCR-ABL1-like group were higher than in the non-BCR-ABL1-like B-others (pfusion-negative BCR-ABL1-like group. The 8-year cumulative incidence of relapse in the fusion-positive BCR-ABL1-like group (35%) was comparable with that in the fusion-negative BCR-ABL1-like group (35%), and worse than in the non-BCR-ABL1-like B-other group (17%, p=0.07). IKZF1 deletions, predominantly other than the dominant-negative isoform and full deletion, co-occurred with tyrosine kinase fusions. This study shows that tyrosine kinase fusion-positive cases are a high-risk subtype of BCP-ALL, which warrants further studies with specific kinase inhibitors to improve outcome.

  15. A task-based assessment of parental occupational exposure to pesticides and childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Gunier, Robert B; Kang, Alice; Hammond, S Katharine; Reinier, Kyndaron; Lea, C Suzanne; Chang, Jeffrey S; Does, Monique; Scelo, Ghislaine; Kirsch, Janice; Crouse, Vonda; Cooper, Robert; Quinlan, Patricia; Metayer, Catherine

    2017-07-01

    Associations between parental occupational pesticide exposure and childhood acute lymphoblastic leukemia (ALL) vary across studies, likely due to different exposure assessment methodologies. We assessed parental occupational pesticide exposure from the year before pregnancy to the child's third year of life for 669 children diagnosed with ALL and 1021 controls. We conducted expert rating using task-based job modules (JM) to estimate exposure to pesticides among farmer workers, gardeners, agricultural packers, and pesticide applicators. We compared this method to (1) partial JM using job titles and a brief description, but without completing the task-based questionnaire, and (2) job exposure matrix (JEM) linking job titles to the International Standard Classifications of Occupation Codes. We used unconditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for ALL cancer risk and pesticide exposure adjusting for child's sex, age, race/ethnicity and household income. Compared to complete JMs, partial JMs and JEM led to 3.1% and 9.4% of parents with pesticide exposure misclassified, respectively. Misclassification was similar in cases and controls. Using complete JMs, we observed an increased risk of ALL for paternal occupational exposure to any pesticides (OR=1.7; 95% CI=1.2, 2.5), with higher risks reported for pesticides to treat nut crops (OR=4.5; 95% CI=0.9, 23.0), and for children diagnosed before five years of age (OR=2.3; 95% CI: 1.3, 4.1). Exposure misclassification from JEM attenuated these associations by about 57%. Maternal occupational pesticide exposure before and after birth was not associated with ALL. The risk of ALL was elevated in young children with paternal occupational pesticide exposure during the perinatal period, using more detailed occupational information for exposure classification. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Immunotargeting relapsed or refractory precursor B-cell acute lymphoblastic leukemia – role of blinatumomab

    Directory of Open Access Journals (Sweden)

    Queudeville M

    2017-07-01

    Full Text Available Manon Queudeville, Rupert Handgretinger, Martin Ebinger Department of Pediatric Hematology and Oncology, University Children’s Hospital, University of Tübingen, Tübingen, Germany Abstract: Patients with refractory or relapsed (R/R acute lymphoblastic leukemia (ALL have a dismal prognosis of around 5% long-term survival when treated with cytotoxic chemotherapy and allogenic stem cell transplantation. T-cell immunobased strategies open up new therapeutic perspectives. Blinatumomab is the first of a new class of antibody constructs that was labeled bispecific T-cell engager (BiTE: it consists of two single chain variable fragment connected with a flexible linker, one side binding CD3, the other CD19. The tight binding and the close proximity to the CD19-positive B-cells and leukemic cells leads to non-major histocompatibility complex-restricted T-cell activation, polyclonal T-cell expansion and direct target cell killing. Applied by continuous infusion, blinatumomab achieves morphological complete response rates ranging from 39% to 69% in R/R ALL patients (compared to 25% after second-line chemotherapy with prolonged overall survival (blinatumomab median overall survival, 7.7 months vs chemotherapy, 4.0 months. In comparison to conventional cytotoxic second-line protocols blinatumomab has a favorable safety profile. The main adverse event is related to the mode of action of blinatumomab: the induction of a cytokine-release syndrome that can be managed by interruption and/or the application of steroids or tocilizumab. Another typical complication is the occurrence of neurological side effects, such as seizures and encephalopathy. This neurotoxicity is reversible after application of steroids and/or withdrawal of blinatumomab. Blinatumomab has proven to be a powerful therapeutic option in R/R ALL patients both adult and pediatric because of its efficacy and limited toxicity. Keywords: R/R precursor B-cell ALL, blinatumomab, T

  17. Effects of malnutrition on oxidative burst functions and infection episodes in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Cakir, F B; Aydogan, G; Timur, C; Canpolat, C; Tulunay, A; Eksioglu Demiralp, E; Berrak, S G

    2012-12-01

    The aim of this study was to determine the effect of malnutrition on oxidative burst functions (OBF) of neutrophils in children with acute lymphoblastic leukemia (ALL). Twenty-eight patients with ALL and thirty healthy controls were enrolled to the study. Thirteen patients with ALL were found to have malnutrition. While neutrophil OBF of ALL patients without malnutrition were studied both before induction chemotherapy and 3 months after, the same functions in ALL patients with malnutrition were studied both before induction chemotherapy and when the nutritional status improved. Control group were studied at admission and 3 months later. The OBF of ALL patients with and without malnutrition before induction chemotherapy were found to be significantly lower than the control group (P = 0.009), whereas the OBF were found to be similar in both patient groups with ALL (P = 0.27). The median infection episode rate and the duration of antibiotics therapy during the study period were similar in both patient groups with ALL. The repeated OBF of both patient groups with ALL were shown to increase to similar values with the control group in the third month of chemotherapy (P = 0.002). The median infection episode rate during the first month of chemotherapy was shown to decrease significantly during the third month of chemotherapy in both patient with ALL groups (P malnutrition on OBF. However, our results still need to be verified via further larger scaled studies of OBF in leukemic children with and without malnutrition. © 2012 Blackwell Publishing Ltd.

  18. Analysis of Thiopurine S-Methyltransferase Deficient Alleles in Acute Lymphoblastic Leukemia Patients in Mexican Patients.

    Science.gov (United States)

    Jiménez-Morales, Silvia; Ramírez-Florencio, Mireya; Mejía-Aranguré, Juan Manuel; Núñez-Enríquez, Juan Carlos; Bekker-Mendez, Carolina; Torres-Escalante, José Luis; Flores-Lujano, Janet; Jiménez-Hernández, Elva; Del Carmen Rodríguez-Zepeda, María; Leal, Yelda A; González-Montalvo, Pablo Miguel; Pantoja-Guillen, Francisco; Peñaloza-Gonzalez, José Gabriel; Gutiérrez-Juárez, Erick Israel; Núñez-Villegas, Nora Nancy; Pérez-Saldivar, Maria Luisa; Guerra-Castillo, Francisco Xavier; Flores-Villegas, Luz Victoria; Ramos-Cervantes, María Teresa; Fragoso, José Manuel; García-Escalante, María Guadalupe; Del Carmen Pinto-Escalante, Doris; Ramírez-Bello, Julián; Hidalgo-Miranda, Alfredo

    2016-11-01

    It has been demonstrated that heterozygote and homozygote thiopurine S-methyltransferase (TPMT) mutant allele carriers are at high risk to develop severe and potentially fatal hematopoietic toxicity after treatment with standard doses of 6-mercaptopurine (6-MP) and methotrexate (MX). Those drugs are the backbone of acute lymphoblastic leukemia (ALL) and several autoimmune disease treatments. We undertook this study to determine the frequency of the TPMT deficient alleles in children with ALL and non-ALL subjects from Mexico City and Yucatan, Mexico. We included 849 unrelated subjects, of which 368 ALL children and 342 non-ALL subjects were from Mexico City, and 60 ALL cases and 79 non-ALL individuals were from Yucatan. Genotyping of the rs1800462, rs1800460 and rs1142345 SNPs was performed by 5'exonuclease technique using TaqMan probes (Life Technologies Foster City, CA). The mutant TPMT alleles were present in 4.8% (81/1698 chromosomes) and only 0.2% were homozygote TPMT*3A/TPMT*3A. We did not find statistically significant differences in the distribution of the mutant alleles between patients from Mexico City and Yucatan in either ALL cases or non-ALL. Nonetheless, the TPMT*3C frequency in ALL patients was higher than non-ALL subjects (p = 0.03). To note, the null homozygous TPMT*3A/TPMT*3A genotype was found in 2.5% of the non-ALL subjects. TPMT mutant alleles did not exhibit differential distribution between both evaluated populations; however, TPMT*3C is overrepresented in ALL cases in comparison with non-ALL group. Assessing the TPMT mutant alleles could benefit the ALL children and those undergoing 6-MP and MX treatment. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  19. Gene Expression Profiling of Acute Lymphoblastic Leukemia in Children with Very Early Relapse.

    Science.gov (United States)

    Núñez-Enríquez, Juan Carlos; Bárcenas-López, Diego Alberto; Hidalgo-Miranda, Alfredo; Jiménez-Hernández, Elva; Bekker-Méndez, Vilma Carolina; Flores-Lujano, Janet; Solis-Labastida, Karina Anastacia; Martínez-Morales, Gabriela Bibiana; Sánchez-Muñoz, Fausto; Espinoza-Hernández, Laura Eugenia; Velázquez-Aviña, Martha Margarita; Merino-Pasaye, Laura Elizabeth; García Velázquez, Alejandra Jimena; Pérez-Saldívar, María Luisa; Mojica-Espinoza, Raúl; Ramírez-Bello, Julián; Jiménez-Morales, Silvia; Mejía-Aranguré, Juan Manuel

    2016-11-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer worldwide. Mexican patients have high mortality rates, low frequency of good prognosis biomarkers (i.e., ETV6-RUNX1) and a high proportion is classified at the time of diagnosis with a high risk to relapse according to clinical features. In addition, very early relapses are more frequently observed than in other populations. The aim of the study was to identify new potential biomarkers associated with very early relapse in Mexican ALL children through transcriptome analysis. Microarray gene expression profiling on bone marrow samples of 54 pediatric ALL patients, collected at time of diagnosis and/or at relapse, was performed. Eleven patients presented relapse within the first 18 months after diagnosis. Affymetrix Human Transcriptome Array 2.0 (HTA 2.0) was used to perform gene expression analysis. Annotation and functional enrichment analyses were carried out using Gene Ontology, KEGG pathway analysis and Ingenuity Pathway Analysis tools. BLVRB, ZCCHC7, PAX5, EBF1, TMOD1 and BLNK were differentially expressed (fold-change >2.0 and p value <0.01) between relapsed and non-relapsed patients. Functional analysis of abnormally expressed genes revealed their important role in cellular processes related to the development of hematological diseases, cancer, cell death and survival and in cell-to-cell signaling interaction. Our data support previous findings showing the relevance of PAX5, EBF1 and ZCCHC7 as potential biomarkers to identify a subgroup of ALL children in high risk to relapse. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  20. Vincristine toxicity with co-administration of fluconazole during induction therapy for pediatric acute lymphoblastic leukemia.

    Science.gov (United States)

    Smitherman, Andrew B; Faircloth, Cassidy B; Deal, Allison; Troy, Michael; Gold, Stuart H

    2017-10-01

    Antifungal prophylaxis is recommended for patients with acute lymphoblastic leukemia (ALL) during high-risk periods such as induction; however, increased vincristine toxicities have been reported with the co-administration of triazole antifungals. We sought to determine whether vincristine-associated toxicities are higher among children with ALL concurrently given fluconazole prophylaxis compared to no prophylaxis. Using a retrospective cohort design, we reviewed records of pediatric patients treated for newly diagnosed ALL from 2003 to 2013. Patients were classified by fluconazole exposure during induction. The development of vincristine-associated toxicity and vincristine dose adjustment were the primary outcomes evaluated. The adjusted risk difference (RD) for vincristine-related toxicity associated with triazole exposure was determined. We identified 197 patients meeting inclusion criteria for evaluation, 160 (81%) of whom received fluconazole prophylaxis. Among patients receiving fluconazole, 36/160 (22%) developed vincristine toxicity compared to 7/37 (19%) among those not receiving prophylaxis (RD: 3%, 95% confidence interval [CI] -11 to 18%). Adjusting for patient age and race, no statistically significant increased risk for vincristine-associated toxicity with fluconazole exposure was observed (RD 5%, 95% CI -8 to 17%). An increased risk for vincristine-associated toxicity was independently associated with age 10 years or older (RD 19%, 95% CI 4-34%). Co-administration of fluconazole during induction therapy for pediatric ALL does not significantly increase the risk for vincristine-associated toxicities; however, patients 10 years or older are at an increased risk for toxicity independent of fluconazole exposure. Prophylaxis with fluconazole during induction therapy for pediatric ALL, if warranted, appears to be a safe clinical practice. © 2017 Wiley Periodicals, Inc.

  1. The treatment of childhood acute lymphoblastic leukemia in Guatemala: Biologic features, treatment hurdles, and results.

    Science.gov (United States)

    Antillón, Federico G; Blanco, Jessica G; Valverde, Patricia D; Castellanos, Mauricio; Garrido, Claudia P; Girón, Veronica; Letona, Tomas R; Osorio, Emilia J; Borrayo, Dyna A; Mack, Ricardo A; Melgar, Mario A; Lorenzana, Rodolfo; Ribeiro, Raul C; Metzger, Monika; Conter, Valentino; Rossi, Emanuela; Valsecchi, Maria Grazia

    2017-02-01

    The National Pediatric Oncology Unit (UNOP) is the only pediatric hemato-oncology center in Guatemala. Patients ages 1 to 17 years with acute lymphoblastic leukemia (ALL) were treated according to modified ALL Intercontinental Berlin-Frankfurt-Münster (IC-BFM) 2002 protocol. Risk classification was based on age, white blood cell count, immunophenotype, genetics (when available), and early response to therapy. From July 2007 to June 2014, 787 patients were treated, including 160 who had standard-risk ALL, 450 who had intermediate-risk ALL, and 177 who had high-risk ALL. The induction death rate was 6.6%, and the remission rate was 92.9%. The rates of death and treatment abandonment during first complete remission were 4.8% and 2.5%, respectively. At a median observation time of 3.6 years, and with abandonment considered an event, the 5-year event-free survival and overall survival estimates ( ± standard error) were 56.2% ± 2.1% and 64.1% ± 2.1%, respectively, with a 5-year cumulative incidence of relapse of 28.9% ± 2.0%. Twenty-one of 281 patients (7.5%) investigated were positive for the ets variant 6/runt-related transcription factor 1 (ETV6/RUNX1) fusion. A well organized center in a low-middle-income country can overcome the disadvantages of malnutrition and reduce abandonment. Outcomes remain suboptimal because of late diagnosis, early death, and a high relapse rate, which may have a partly genetic basis. Earlier diagnosis, better management of complications, and better knowledge of ALL will improve outcomes. Cancer 2017;123:436-448. © 2016 American Cancer Society. © 2016 American Cancer Society.

  2. Hypertriglyceridemia during asparaginase treatment in children with acute lymphoblastic leukemia correlates with antithrombin activity in adolescents.

    Science.gov (United States)

    Persson, Lisa; Harila-Saari, Arja; Hed Myrberg, Ida; Heyman, Mats; Nilsson, Anna; Ranta, Susanna

    2017-10-01

    Asparaginase (ASP) is a cornerstone in the treatment of acute lymphoblastic leukemia (ALL). It is also known for its ability to cause side effects, such as allergy and pancreatitis, as well as lipid and coagulation disturbances. The most important laboratory abnormalities are hypertriglyceridemia (HTG) and low antithrombin (AT). HTG is usually considered to be transient and benign in children with ALL, whereas low AT activity predisposes to thrombosis. Studies on the incidence and significance of HTG in children with ALL are scarce, and their findings have not always been congruent. We investigated the incidence and significance of ASP-related HTG, defined as triglyceride values more than five times the upper normal limit, in children with ALL. We analyzed the laboratory and clinical data of children diagnosed with ALL at the Karolinska Hospital, Stockholm, Sweden, from July 2008 to December 2014. Triglyceride and AT values were measured before each injection of pegylated ASP. The study group comprised of 92 patients, aged 1-17.9 years at diagnosis (median 4.8 years), almost half (42/92, 46%) of whom had HTG. A significant negative correlation between triglyceride and AT values was observed in those aged over 10 years (P = 0.0002). No significant correlation was found between HTG and thrombosis, osteonecrosis, or pancreatitis. Although common, ASP-associated HTG was not associated with other ASP-related toxicities. HTG correlated with decreased AT activity in older children, which may explain previous association between HTG and thrombosis. Larger studies are of interest with regard to establishing guidelines for HGT management. © 2017 Wiley Periodicals, Inc.

  3. Predictors of diagnostic interval and associations with outcome in acute lymphoblastic leukemia.

    Science.gov (United States)

    Gupta, Sumit; Gibson, Paul; Pole, Jason D; Sutradhar, Rinku; Sung, Lillian; Guttmann, Astrid

    2015-06-01

    Little is known about diagnostic interval lengths in childhood cancer, their predictors or impact upon survival. To date, studies have relied on questionnaires or chart abstraction. We aimed to construct and validate a diagnostic interval measure using health services data among children with acute lymphoblastic leukemia (ALL) in order to determine predictors of prolonged intervals and associations with event-free survival (EFS). All children with ALL diagnosed 1995-2011 (N = 1,541) in Ontario, Canada were linked to population-based health administrative databases. Healthcare claims prior to diagnosis were used to define healthcare episodes. Diagnostic intervals (time between first episode with diagnostic code a priori classified as consistent with underlying ALL, and diagnosis) were validated by correlation with a chart abstraction-based measure. Intervals were generally short (median 2 days, IQR 1-3). Predictors of longer intervals included having general primary care physicians versus pediatricians (odds ratio 1.60, 95%CI 1.04-2.47; P = 0.03). While prolonged diagnostic intervals were associated with superior EFS (hazard ratio 0.71, 95%CI 0.52-0.98; P = 0.04), this was explained by confounding by disease biology. Health administrative data can be used to measure diagnostic intervals in ALL and potentially other pediatric malignant and non-malignant diseases. Diagnostic intervals were short and a marker of disease severity rather than independent predictors of outcome. These findings may be used to address caregiver guilt and caution against "early diagnosis" benchmarks not based in evidence. Future studies should examine the impact of diagnostic interval length in other conditions, but should account for potential confounding by disease severity. © 2015 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    Caniza, Miguela A; Hunger, Stephen P; Schrauder, Andre; Valsecchi, Maria Grazia; Pui, Ching-Hon; Masera, Giuseppe

    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. We retrospectively reviewed mortality due to varicella in the records of 15 pediatric ALL study groups throughout Europe, Asia, and North America during the period 1984-2008. We found that 20 of 35,128 children with ALL (0.057%; 95% confidence interval [CI], 0.037-0.088%) died of VZV infection. The mortality rate was lower in North America (3 of 11,558 children, 0.026%; 95% CI, 0.009-0.076%) than in the Asian countries (2 of 4,882 children, 0.041%; 95% CI, 0.011-0.149%) and in Europe (15 of 18,688 children, 0.080%; 95% CI, 0.049-0.132%) consistent with the generally higher rate of VZV vaccination in North America. Fourteen of the 20 patients (70%) died during the first year of treatment for ALL. One death was attributed to varicella vaccination. The negligible rate of fatal varicella infection in children with ALL, the risk that accompanies vaccination, and the necessity of withholding chemotherapy for vaccination appear to outweigh the potential benefit of varicella vaccination for children during treatment of ALL. Copyright © 2010 Wiley Periodicals, Inc.

  5. 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

  6. Impaired mitochondrial function is abrogated by dexrazoxane in doxorubicin-treated childhood acute lymphoblastic leukemia survivors.

    Science.gov (United States)

    Lipshultz, Steven E; Anderson, Lynn M; Miller, Tracie L; Gerschenson, Mariana; Stevenson, Kristen E; Neuberg, Donna S; Franco, Vivian I; LiButti, Daniel E; Silverman, Lewis B; Vrooman, Lynda M; Sallan, Stephen E

    2016-03-15

    Impaired cardiac function in doxorubicin-treated childhood cancer survivors is partly mediated by the disruption of mitochondrial energy production. Doxorubicin intercalates into mitochondrial DNA (mtDNA) and disrupts genes encoding for polypeptides that make adenosine triphosphate. This cross-sectional study examined mtDNA copy numbers per cell and oxidative phosphorylation (OXPHOS) in peripheral blood mononuclear cells (PBMCs) in 64 childhood survivors of high-risk acute lymphoblastic leukemia (ALL) who had been treated on Dana-Farber Cancer Institute childhood ALL protocols and had received doxorubicin alone (42%) or doxorubicin with the cardioprotectant dexrazoxane (58%). The number of mtDNA copies per cell and the OXPHOS enzyme activity of nicotinamide adenine dinucleotide dehydrogenase (complex I [CI]) and cytochrome c oxidase (complex IV [CIV]) were measured with quantitative real-time polymerase chain reaction immunoassays and thin-layer chromatography, respectively. At a median follow-up of 7.8 years after treatment, the median number of mtDNA copies per cell for patients treated with doxorubicin alone (1106.3) was significantly higher than the median number for those who had also received dexrazoxane (310.5; P = .001). No significant differences were detected between the groups for CI or CIV activity. Doxorubicin-treated survivors had an increased number of PBMC mtDNA copies per cell, and concomitant use of dexrazoxane was associated with a lower number of mtDNA copies per cell. Because of a possible compensatory increase in mtDNA copies per cell to maintain mitochondrial function in the setting of mitochondrial dysfunction, overall OXPHOS activity was not different between the groups. The long-term sustainability of this compensatory response in these survivors at risk for cardiac dysfunction over their lifespan is concerning. © 2016 American Cancer Society.

  7. The Relationship Between Risk Factors and Survival in Adult Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Allahyari, Abolghasem; Hashemi, Seyed-Mehdi; Nazemian, Fahimeh; Karimi, Mohammad; Kazemi, Mohammad-Reza; Sadeghi, Masoud

    2016-08-01

    Acute lymphoblastic leukemia (ALL) is aggressive cancer, especially in adults as only 20-40% is cured with current treatment regimens. The aim of this study is to evaluate prognostic factors and their effects on survival in ALL patients in the Northeast of Iran. In a descriptive and retrospective study from 2009 to 2015, 48 ALL patients referred to hematology-oncology clinic. Age, sex, fever, blood group, type of ALL and consumption of amphotericin B, forms of cytogenetic, survival in the patients, WBC, hemoglobin, and platelet were checked in the first referral for every patient. The mean follow-up was 27.3 months in which 28 patients (59.3%) died. overall survival (OS) was plotted by GraphPad Prism 5 and the Log-rank test was used for analysis of survival with risk factors. The mean age for all the ALL patients at diagnosis was 32.3 years (range, 15-71 years), and 81.3% were male. Of all patients, 62.5% had fever and 25% consumed amphotericin B. 1-, 2-, 3-, 4-, 5-year OS rates were 62.2%, 52.7%, 40.6%, 39.1%, 22.2%, respectively. 75%, 29.2% and 39.6% of patients had WBC 35 years is the most prognostic factor in ALL patients. Also, patients who received amphotericin B had lower life expectancy because these patients were suffering from fungal infection or due to lack of response to antibacterial drugs, they have been treated with amphotericin B.

  8. [Minor phenotypic variants in patients with acute lymphoblastic leukemia from west Mexico].

    Science.gov (United States)

    Estrada-Padilla, S A; Corona-Rivera, J R; Sánchez-Zubieta, F; Bobadilla-Morales, L; Corona-Rivera, A

    2015-02-01

    Acute lymphoblastic leukemia (ALL) has been associated with an excess of minor phenotypic variants (MPV), including common variants and minor anomalies, indicative of an altered phenogenesis. The objective of the study was to determine the association between MPV and ALL. In a hospital based case-control study, we studied 120 children with ALL (including standard and high risk) and 120 healthy children as a control group, matched for age and sex, seen in the Hospital Civil de Guadalajara Dr. Juan I. Menchaca (Guadalajara, Mexico). In both groups, 28 anthropometric measurements were made, as well as a systematic search for 405 MPV, through a physical examination. Adjusted odds ratio was estimated (aOR) with its intervening variables by logistic regression. The confidence interval was 95% (95%CI). Anthropometric signs associated with ALL were: long upper segment (aOR= 2.19, 95%CI: 1.01-4.76), broad jaw (aOR= 2.62, 95%CI: 1.29-5.30), narrow ears (aOR= 6.22, 95%CI: 2.60-14.85), and increase in internipple distance (aOR= 2.53, 95%CI: 1.07-5.98). The hypoplasia mesofacial, broad forehead, small nose, short columella, narrow ears, telethelia, Sydney crease (SC), Greek type feet and café-au-lait spots (CALS), had a 3 to 17 times higher frequency in children with ALL. By number, an association was found from ≥4 MPV (aOR= 2.14, 95%CI: 1.25-3.66, P=.004). From ≥4 MPV, an association was found with ALL, suggesting prenatal factors in phenogenesis and leukemogenesis. CALS and SC were confirmed as MPV in children with ALL. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  9. Medication errors on oral chemotherapy in children with acute lymphoblastic leukemia in a developing country.

    Science.gov (United States)

    Oberoi, Sapna; Trehan, Amita; Marwaha, Ram Kumar

    2014-12-01

    Medication errors occur universally. Inappropriate administration of chemotherapy drugs can have adverse effects in cancer patients. Our objective was to assess the rate and type of medication errors in children with acute lymphoblastic leukemia (ALL) receiving oral chemotherapy in outpatient setting. Prescription and administration of oral chemotherapy drugs in children with ALL were evaluated prospectively to determine rate and type of medication errors. Errors were defined as prescription (physician) level or administration (patient) level errors. Two hundred eighty-nine drugs were prescribed to 121 patients. Medication errors occurred in 36 (12.5%) prescriptions; 21(7.3%) were administration errors, 13 (4.5%) were prescribing errors, and two errors occurred at both levels. Mercaptopurine (6-MP) was significantly associated with higher rates of errors (Odds ratio [OR] = 2.1, 95% CI [confidence interval] 1-4.1) whereas lapses were less with dexamethasone (OR = 0.25, 95% CI 0.09-0.67). As a result of medication errors 28 (23.1%) patients received inappropriate doses. Twenty five (21%) patients received sub-optimal doses whereas three got higher doses of chemotherapy. On univariate analysis, socioeconomic status, education status of the caregiver, 6-MP and methotrexate were significantly associated with errors (P ≤ 0.05). On multivariate analysis, ≤ primary school education of the caregiver and prescription of methotrexate were independent predictors of errors. Medication errors affected nearly one fourth of the children receiving oral chemotherapy. Future studies are needed to look at effective interventions to avoid chemotherapy associated errors especially amongst the lower strata of society. © 2014 Wiley Periodicals, Inc.

  10. Impact of TCF3 rearrangement on CNS relapse in egyptian pediatric acute lymphoblastic leukemia.

    Science.gov (United States)

    ElGendi, Hoda M; Abdelmaksoud, Abeer A; Eissa, Doaa G; Abusikkien, Samy A

    2014-10-01

    TCF3 rearrangement mostly t(1;19) (q23;p13)/ TCF3-PBX1 gene is associated with favorable outcome in acute lymphoblastic leukemia (ALL) upon treatment with intensification protocols; however, it is associated with higher incidence of central nervous system (CNS) relapse which may affect outcome of patients. We aimed to assess TCF3 rearrangement in newly diagnosed pediatric ALL patients in relation to clinical and laboratory parameters, CNS relapse, and clinical outcome. Eighty newly diagnosed pediatric ALL patients following at Pediatric Hematology Oncology Clinic, Ain Shams University Hospitals were included in this study. Their ages ranged from 0.75 to 16 years. Seventy six (95%) patients had B-lineage ALL and four (5%) had T-lineage ALL. Data recorded included; age, sex, extramedullary manifestations, CNS, and testes infiltrations, risk stratification, response to treatment, and CBC and BM findings. TCF3 rearrangement was assessed by FISH technique using dual color break-apart probe. TCF3 rearrangement [t(1;19) (q23;p13)] was detected in 16 (20%) out of the 80 studied patients, and it was significantly associated with splenomegaly, lymphadenopathy, CNS infiltration at presentation, high total leucocytic count, low platelet count, high-risk group, and isolated CNS relapse. These results identify a group of high-risk ALL patients with high incidence of CNS relapse and poor response to standard therapeutic regimen. Analysis of TCF3 rearrangement [t(1;19) (q23;p13)] at diagnosis may provide a valuable target for modified and intensified CNS-directed chemotherapeutic protocol aiming to improve the patients' outcome.

  11. Clinical significance of thymidine kinase in Egyptian children with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Adel A Hagag

    2015-01-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common childhood malignancy, representing one-third of pediatric cancers. Thymidine kinase-1 (TK-1 is expressed in proliferating cells so elevated TK-1 indicates active tumor growth. Objective: To study the clinical significance of TK-1 in children with ALL. Patients and Methods: This study was carried out on 40 children with newly diagnosed ALL who were admitted to Oncology Unit, Pediatric department, Tanta University (26 males and 14 females with their ages ranged from 4 to 10 years and 30 healthy children of matched age and sex as a control group. For all patients the following were done: Complete blood picture, bone marrow examination, immunophenotyping and TK-1 serum levels. Results: Mean TK-1 level was significantly higher in patients at diagnosis than controls and significantly higher in patients with unfavorable outcome than patients with favorable outcome. Mean TK-1 level was significantly higher in patients in relapse than patients in remission and controls. No significant differences in mean TK-1 level between patients in remission and controls. There were statistically significant differences in disease free survival and overall survival between patients with favorable and unfavorable outcome. Conclusion: From this study we concluded that TK is a helpful marker in diagnosis and follow-up of patients with ALL. Recommendations: Thymidine kinase-1 should be routinely assessed at diagnosis and during follow-up in ALL patients for better diagnostic and prognostic assessment and should be taken in consideration in designing future therapeutic strategies based on patients-specific risk factors.

  12. B-cell precursor acute lymphoblastic leukemia and stromal cells communicate through Galectin-3

    Science.gov (United States)

    Fei, Fei; Joo, Eun Ji; Tarighat, Somayeh S.; Schiffer, Isabelle; Paz, Helicia; Fabbri, Muller; Abdel-Azim, Hisham; Groffen, John; Heisterkamp, Nora

    2015-01-01

    The molecular interactions between B-cell precursor acute lymphoblastic leukemia (pre-B ALL) cells and stromal cells in the bone marrow that provide microenvironmentally-mediated protection against therapeutic drugs are not well-defined. Galectin-3 (Lgals3) is a multifunctional galactose-binding lectin with reported location in the nucleus, cytoplasm and extracellular space in different cell types. We previously reported that ALL cells co-cultured with stroma contain high levels of Galectin-3. We here establish that, in contrast to more mature B-lineage cancers, Galectin-3 detected in and on the ALL cells originates from stromal cells, which express it on their surface, secrete it as soluble protein and also in exosomes. Soluble and stromal-bound Galectin-3 is internalized by ALL cells, transported to the nucleus and stimulates transcription of endogenous LGALS3 mRNA. When human and mouse ALL cells develop tolerance to different drugs while in contact with protective stromal cells, Galectin-3 protein levels are consistently increased. This correlates with induction of Galectin-3 transcription in the ALL cells. Thus Galectin-3 sourced from stroma becomes supplemented by endogenous Galectin-3 production in the pre-B ALL cells that are under continuous stress from drug treatment. Our data suggest that stromal Galectin-3 may protect ALL cells through auto-induction of Galectin-3 mRNA and tonic NFκB pathway activation. Since endogenously synthesized Galectin-3 protects pre-B ALL cells against drug treatment, we identify Galectin-3 as one possible target to counteract the protective effects of stroma. PMID:25869099

  13. Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)-rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study

    DEFF Research Database (Denmark)

    Mann, Georg; Attarbaschi, Andishe; Schrappe, Martin

    2010-01-01

    To define a role for hematopoietic stem cell transplantation (HSCT) in infants with acute lymphoblastic leukemia and rearrangements of the mixed-lineage-leukemia gene (MLL(+)), we compared the outcome of MLL(+) patients from trial Interfant-99 who either received chemotherapy only or HSCT. Of 376....... In summary, HSCT seems to be a valuable option for a subgroup of infant MLL(+) acute lymphoblastic leukemia carrying further poor prognostic factors. The trial was registered at www.clinicaltrials.gov as #NCT00015873 and at www.controlled-trials.com as #ISRCTN24251487....

  14. Intensive treatment of children with acute lymphoblastic leukemia according to ALL-BFM-86 without cranial radiotherapy : Results of Dutch Childhood Leukemia Study Group protocol ALL-7 (1988-1991)

    NARCIS (Netherlands)

    Kamps, WA; Bokkerink, JPM; Hahlen, K; Hermans, J; Riehm, H; Gadner, H; Schrappe, M; Slater, R; van den Berg-de Ruiter, E; Smets, LA; de Vaan, GAM; Weening, RS; van Weerden, JF; van Wering, ER; van der Does-van den Berg, A

    1999-01-01

    In The Netherlands from July 1988 to October 1991, children (0 to 16 years of age) with de novo acute lymphoblastic leukemia (ALL) were treated according to protocol ALL-7 of the Dutch Childhood Leukemia Study Group (DCLSG). In this protocol, chemotherapy and treatment stratification were identical

  15. Avascular necrosis of the femoral head in children with acute lymphoblastic leukemia: a 4- to 9-year follow-up study.

    Science.gov (United States)

    Madadi, Firooz; Shamsian, Bibi Shahin; Alavi, Samin; Madadi, Firoozeh; Eajazi, Alireza; Aslani, Afshin

    2011-10-05

    Avascular necrosis of the femoral head is usually seen in children aged 1.5 to 10 years, reaching a peak incidence between the ages of 4 and 9. Avascular necrosis of the femoral head is a known complication of corticosteroid therapy in acute lymphoblastic leukemia. There are few reports in the literature regarding the natural history of this condition, and there is no consensus on its management. This study examined the natural history of avascular necrosis of the femoral head in children with leukemia. From 1993 to 2006, a total of 865 children with acute lymphoblastic leukemia were admitted to the hematology-oncology ward of a children's hospital. The diagnosis of acute lymphoblastic leukemia was established by bone marrow aspiration. Based on clinical and radiographic findings, avascular necrosis of the femoral head was found in 7 patients; these patients underwent follow-up for 4 to 9 years. Avascular necrosis of the femoral head was clinically symptomatic in all of the children, and they had advanced radiographic collapse of the femoral head. However, the head of the femur was not at risk in any patient based on clinical and radiographic findings. Patients received supportive treatment such as abduction brace and physiotherapy. After 4 to 9 years of follow-up, clinical and radiographic results were satisfactory. Provided that the head of the femur is not at risk, avascular necrosis of the femoral head in children with acute lymphoblastic leukemia may be successfully managed with nonoperative care. Copyright 2011, SLACK Incorporated.

  16. BFM-oriented treatment for children with acute lymphoblastic leukemia without cranial irradiation and treatment reduction for standard risk patients : results of DCLSG protocol ALL-8 (1991-1996)

    NARCIS (Netherlands)

    Kamps, WA; Bokkerink, JPM; Hakvoort-Cammel, FGAJ; Veerman, AJP; Weening, RS; van Wering, ER; van Weerden, JF; Hermans, J; Slater, R; van den Berg, E; Kroes, WG; van der Does-van den Berg, A

    Modern treatment strategies, consisting of intensive chemotherapy and cranial irradiation, have remarkably improved the prognosis for children with acute lymphoblastic leukemia. However, patients with a potential for cure are at risk of severe acute and late adverse effects of treatment.

  17. Neutropenic enterocolitis as a presenting complication of acute lymphoblastic leukemia: an unusual case marked by delayed perforation of the descending colon.

    Science.gov (United States)

    Wilson, David B; Rao, Aarati; Hulbert, Monica; Mychaliska, Kerry P; Luchtman-Jones, Lori; Hill, D Ashley; Foglia, Robert P

    2004-07-01

    Neutropenic enterocolitis (NE) is a life-threatening complication most commonly seen in patients receiving intensive chemotherapy for acute leukemia. The condition usually affects the terminal ileum, cecum, or ascending colon. In rare instances, NE may occur before the initiation of chemotherapy or involve more distal bowel. The authors report the case of a 2-year-old girl who had NE affecting the descending colon as a presenting complication of acute lymphoblastic leukemia. Despite aggressive medical interventions, including granulocyte infusions, she had a delayed bowel perforation that was managed successfully with surgery. This case highlights the challenges of treating patients who have NE as an initial manifestation of acute leukemia.

  18. Acute Myeloid Leukemia in Childhood

    OpenAIRE

    Yöntem, Ahmet; Bayram, İbrahim

    2018-01-01

    Acute leukemia is basically divided intoacute lymphoblastic leukemia and acute myeloid leukemia. About 15-20% ofchildhood leukemia is caused by acute myeloid leukemia.AML is classified according to morphological, cytochemical and immunophenotypiccharacteristics. AML patients may present with various clinical signsand symptoms due to leukemic cell infiltration. Age, gender, race, structuralfeatures of the patient and cytogenetic abnormalities are important factorsaffecting prognosis in AML. Th...

  19. 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.

  20. on Lymphoblastic Leukemia Jurkat Cells

    African Journals Online (AJOL)

    Purpose: To evaluate the cytotoxic effect of ethanol extract of aerial parts of Convolvulus arvensis against lymphoblastic leukemia, Jurkat cells. Methods: The aerial parts of C. arvensis were collected, identified, powdered and soaked in ethanol. The extract was filtered and evaporated, and the residue assessed for cytotoxic ...

  1. Outcome After First Relapse in Children With Acute Lymphoblastic Leukemia : A Report Based on the Dutch Childhood Oncology Group (DCOG) Relapse ALL 98 Protocol

    NARCIS (Netherlands)

    van den Berg, H.; de Groot-Kruseman, H. A.; Damen-Korbijn, C. M.; de Bont, E. S. J. M.; Schouten-van Meeteren, A. Y. N.; Hoogerbrugge, P. M.

    Background. We report on the treatment of children and adolescents with acute lymphoblastic leukemia (ALL) in first relapse. The protocol focused on: (1) Intensive chemotherapy preceding allogeneic stem cell transplantation (SCT) in early bone marrow relapse; (2) Rotational chemotherapy in late

  2. Minimal residual disease levels in bone marrow and peripheral blood are comparable in children with T cell acute lymphoblastic leukemia (ALL), but not in precursor-B-ALL

    NARCIS (Netherlands)

    van der Velden, VHJ; Jacobs, DCH; Wijkhuijs, AJM; Comans-Bitter, WM; Willemse, MJ; Hahlen, K; Kamps, WA; van Wering, ER; van Dongen, JJM

    Sensitive and quantitative detection of minimal residual disease (MRD) in bone marrow (BM) samples of children with acute lymphoblastic leukemia (ALL) is essential for evaluation of early treatment response. In this study, we evaluated whether the traumatic BM samplings can be replaced by peripheral

  3. G80A Single Nucleotide Polymorphism in Reduced Folate Carrier-1 Gene in a Mexican Population and its Impact on Survival in Patients with Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Candelaria, Myrna; Ojeda, Juan; Gutiérrez-Hernández, Olga; Taja-Chayeb, Lucia; Vidal-Millán, Silvia; Dueñas-González, Alfonso

    2016-01-01

    Hyper-CVAD is the treatment for patients with acute lymphoblastic leukemia in our institution. To evaluate the impact of single nucleotide polymorphisms at genes associated with methotrexate metabolism on survival. The presence of the single nucleotide polymorphisms G80A at reduced folate carrier-1 gene and C677T in the methylenetetrahydrofolate reductase gene was determined by denaturing high performance liquid chromatography and validated by sequencing. Both single nucleotide polymorphisms were evaluated in 71 healthy donors and in an exploratory pilot trial with acute lymphoblastic leukemia patients to determine the influence of these single nucleotide polymorphisms on clinical outcome. Clinical characteristics, response, and outcome were registered. A Cox regression analysis was done to evaluate factors influencing response and overall survival. There were no differences in the frequency of single nucleotide polymorphisms between volunteers and acute lymphoblastic leukemia patients according to the Hardy-Weinberg test. Sensitivity and specificity were 72 and 91% for the G80A, and 64 and 75% for the C677T, respectively. The multivariate analysis showed that the T-immunophenotype and the presence of single nucleotide polymorphism G80A reduced folate carrier-1 were associated with a shorter relapse-free survival and overall survival. The presence of G80A single nucleotide polymorphism at reduced folate carrier-1 gene in acute lymphoblastic leukemia patients was associated with a poorer prognosis.

  4. Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: A prospective sibling donor versus no-donor comparison

    NARCIS (Netherlands)

    J.J. Cornelissen (Jan); B. van der Holt (Bronno); G.E.G. Verhoef (Gregor); M.B. van 't Veer (Mars); M.H.J. van Oers (Marinus); G.J. Ossenkoppele (Gert); P. Sonneveld (Pieter); J. Maertens (Johan); M. van Marwijk Kooy (Marinus); M.R. Schaafsma (Martijn); P.W. Wijermans (Pierre); D.H. Biesma (Douwe); S. Wittebol (Shulamit); P.J. Voogt (Paul); J.W. Baars (Joke); P. Zachée (Pierre); L.F. Verdonck (Leo); B. Löwenberg (Bob); A.W. Dekker (Adriaan)

    2009-01-01

    textabstractWhile commonly accepted in poor-risk acute lymphoblastic leukemia (ALL), the role of allogeneic hematopoietic stem cell transplantation (allo-SCT) is still disputed in adult patients with standard-risk ALL. We evaluated outcome of patients with ALL in first complete remission (CR1),

  5. Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison

    NARCIS (Netherlands)

    Cornelissen, Jan J.; van der Holt, Bronno; Verhoef, Gregor E. G.; van't Veer, Mars B.; van Oers, Marinus H. J.; Schouten, Harry C.; Ossenkoppele, Gert; Sonneveld, Pieter; Maertens, Johan; van Marwijk Kooy, Marinus; Schaafsma, Martijn R.; Wijermans, Pierre W.; Biesma, Douwe H.; Wittebol, Shulamit; Voogt, Paul J.; Baars, Joke W.; Zachée, Pierre; Verdonck, Leo F.; Löwenberg, Bob; Dekker, Adriaan W.

    2009-01-01

    While commonly accepted in poor-risk acute lymphoblastic leukemia (ALL), the role of allogeneic hematopoietic stem cell transplantation (allo-SCT) is still disputed in adult patients with standard-risk ALL. We evaluated outcome of patients with ALL in first complete remission (CR1), according to a

  6. What is the relevance of Ikaros gene deletions as a prognostic marker in pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia?

    National Research Council Canada - National Science Library

    Chiara Palmi; Maria Grazia Valsecchi; Giulia Longinotti; Daniela Silvestri; Valentina Carrino; Valentino Conter; Giuseppe Basso; Andrea Biondi; Geertruy Te Kronnie; Giovanni Cazzaniga

    2013-01-01

    .... We focused our analysis on Ikaros (IKZF1) gene deletions in a homogeneous cohort of 410 pediatric patients with Philadelphia chromosome-negative, B-cell precursor acute lymphoblastic leukemia enrolled in Italy into the AIEOP-BFM ALL2000 study...

  7. 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 ...

  8. 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

  9. 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.

  10. Slight cognitive impairment and magnetic resonance imaging abnormalities but normal school levels in children treated for acute lymphoblastic leukemia with chemotherapy only

    NARCIS (Netherlands)

    Kingma, A; van Dommelen, RI; Mooyaart, EL; Willmink, J; Deelman, BG; Kamps, WA

    Objectives: To investigate persistent neuropsychologic late effects in children treated for acute lymphoblastic leukemia at a young age with chemotherapy only by means of serial neuropsychologic assessments (NPAs), magnetic resonance imaging (MRI) of the brain, and evaluation of school levels. Study

  11. Effect of IKZF1 deletions on signal transduction pathways in Philadelphia chromosome negative pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL)

    NARCIS (Netherlands)

    van der Sligte, Naomi E; Scherpen, Frank J G; Ter Elst, Arja; Guryev, Victor; van Leeuwen, Frank N; de Bont, Eveline S J M

    2015-01-01

    BACKGROUND: IKZF1 deletions are an unfavorable prognostic factor in children with Philadelphia chromosome positive (Ph(+)) as well as negative (Ph(-)) acute lymphoblastic leukemia (ALL). Although IKZF1 deletions occur in 10-15% of Ph(-) ALL cases, effects of IKZF1 deletions on signaling pathways in

  12. 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...

  13. 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

  14. 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

  15. IKZF1 DELETIONS ARE INDEPENDENT PROGNOSTIC FACTOR IN PEDIATRIC B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    G. A. Tsaur

    2016-01-01

    Full Text Available We assessed the prognostic significance of IKZF1 gene deletions in 141 pediatric patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL  on Russian multicenter trial in pediatric clinics of Ekaterinburg and Orenburg. IKZF1 deletions were estimated by multiplex ligation-dependent probe amplification. IKZF1 deletions were revealed in 15 (10.6 % patients. IKZF1 deletions were associated with age older than 10 years (p = 0.007, initial white blood cell count higher than 30 × 109/l (p = 0.003, t(9;22(q34.q11 (p = 0.003 and delayed blast clearance: М3 status of bone marrow at day 15 of remission induction (p = 0.003, lack of hematological remission at day 36 (p < 0.001 and high levels of minimal residual disease at days 15, 36 and 85 (p = 0.014; p < 0.001; p = 0.001 correspondingly. Patients with IKZF1 deletions had significantly lower event-free survival (EFS (0.30 ± 0.15 vs 0.89 ± 0.03; p < 0.001 and overall survival (OS (0.44 ± 0.19 vs 0.93 ± 0.02; p < 0.001, while cumulative incidence of relapse was higher (0.67 ± 0.18 vs 0.07 ± 0.02; p < 0.001. In the multivariate analysis IKZF1 deletions were associated with decreased EFS (hazard ratio (HR 4.755; 95 % confidence interval (CI 1.856–12.185; p = 0.001, and OS (HR 4.208; 95 % CI 1.322–13.393; p = 0.015, but increased relapse risk (HR 9,083; 95 % CI 3.119–26.451; p < 0.001. IKZF1 deletions retained their prognostic significance in the intermediate risk group patients (p < 0.001, but not in standard or high-risk groups. Majority of IKZF1 deletions – 12 (80 % of 15 – were revealed in the “B-other” group (n = 83. In this cohort of patients IKZF1 deletions led to inferior EFS (HR 6.172; 95 % CI 1.834–20.767; p = 0.003 and higher relapse rate (HR 16.303; 95 % CI 3.324–79.965; p = 0.015. Thus, our results showed that IKZF1 deletions are independent risk factor in BCP-ALL patients.

  16. HLA complex-linked heat shock protein genes and childhood acute lymphoblastic leukemia susceptibility.

    Science.gov (United States)

    Ucisik-Akkaya, Esma; Davis, Charronne F; Gorodezky, Clara; Alaez, Carmen; Dorak, M Tevfik

    2010-09-01

    Three heat shock protein 70 (HSP70) genes, HSPA1L, HSPA1A, and HSPA1B, are located within the human leukocyte antigen (HLA) class III region. HSPs act as stress signals and regulate natural killer cell response to cancer. HSP70 gene polymorphisms show disease associations partly due to their linkage disequilibrium with HLA alleles. To systematically evaluate their associations with childhood acute lymphoblastic leukemia (ALL), we examined the three functional single nucleotide polymorphisms (SNPs) rs2227956 (T493M) in HSPA1L, rs1043618 in HSPA1A 5'UTR, and rs1061581 (Q351Q) in HSPA1B by TaqMan assays or polymerase chain reaction-restriction fragment length polymorphism in 114 ALL cases and 414 controls from Wales (UK), in 100 Mexican Mestizo ALL cases and 253 controls belonging to the same ethnic group, and in a panel of 82 HLA-typed reference cell line samples. Homozygosity for HSPA1B rs1061581 minor allele G was associated with protection (odds ratio (OR) = 0.37, 95% confidence interval (CI) = 0.16-0.78; P = 0.007) with gene-dosage effect (additive model) reaching significance (P = 0.0001) in the Welsh case-control group. This association was replicated in the second case-control group from Mexico (OR (recessive model) = 0.49, 95% CI = 0.24-0.96; P = 0.03), and the pooled analysis yielded a strong association (Mantel-Haenszel OR = 0.43, 95% CI = 0.27-0.69, P = 0.0004). The association was stronger in males in each group and in the pooled analysis. A three-SNP haplotype including the major allele A of rs1061581 showed a highly significant increase in Welsh cases compared with respective controls (6.7% vs 1.8%; P = 0.0003) due to the difference between male cases and controls. The protective allele of rs1061581 occurred more frequently on the HLA-DRB3 haplotypes (especially DRB1*03) in the cell line panel, but the HSPA1B association was independent from the HLA-DRB4 association previously detected in the same case-control group from Wales (adjusted P = 0

  17. NF-κB in T-cell Acute Lymphoblastic Leukemia: Oncogenic Functions in Leukemic and in Microenvironmental Cells

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Nuno R. dos, E-mail: nrsantos@ualg.pt; Ghezzo, Marinella N.; Silva, Ricardo C. da; Fernandes, Mónica T. [IBB-Institute for Biotechnology and Bioengineering, Centre for Molecular and Structural Biomedicine (CBME), University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal)

    2010-11-05

    Two main NF-κB signaling pathways, canonical and noncanonical, performing distinct functions in organisms have been characterized. Identification of mutations in genes encoding components of these NF-κB signaling pathways in lymphoid malignancies confirmed their key role in leukemogenesis. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes that despite significant therapeutic advances can still be fatal. Although mutations in NF-κB genes have not been reported in T-ALL, NF-κB constitutive activation in human T-ALL and in acute T-cell leukemia mouse models has been observed. Although these studies revealed activation of members of both canonical and noncanonical NF-κB pathways in acute T-cell leukemia, only inhibition of canonical NF-κB signaling was shown to impair leukemic T cell growth. Besides playing an important pro-oncogenic role in leukemic T cells, NF-κB signaling also appears to modulate T-cell leukemogenesis through its action in microenvironmental stromal cells. This article reviews recent data on the role of these transcription factors in T-ALL and pinpoints further research crucial to determine the value of NF-κB inhibition as a means to treat T-ALL.

  18. The cellular senescence of leukemia-initiating cells from acute lymphoblastic leukemia is postponed by ?-Arrestin1 binding with P300-Sp1 to regulate hTERT transcription

    OpenAIRE

    Liu, Shan; Liu, Haiyan; Qin, Ru; Shu, Yi; Liu, Zhidai; Zhang, Penghui; Duan, Caiwen; Hong, Dengli; Yu, Jie; Zou, Lin

    2017-01-01

    Although we previously reported that the self-renewal of leukemia-initiating cells of B-lineage acute lymphoblastic leukemia (B-ALL LICs) was regulated by ?-Arrestin1, a multiple-function protein, the cellular senescence is critical for LICs fate and leukemia progress, and worthy for further investigation. Here we found that depletion of ?-Arrestin1 extended the population doubling time and the percentage of senile cells, the signatures of cellular senescence, of B-ALL LICs. Moreover, lack of...

  19. Racial disparities in the survival of American children, adolescents, and young adults with acute lymphoblastic leukemia, acute myelogenous leukemia, and Hodgkin lymphoma.

    Science.gov (United States)

    Kahn, Justine M; Keegan, Theresa H M; Tao, Li; Abrahão, Renata; Bleyer, Archie; Viny, Aaron D

    2016-09-01

    Race-based survival in children and adolescents with hematologic malignancies has been a national challenge for decades. Large-scale investigations of age- and race-based survival trends over time in these patients have not previously been reported. The objective of this study was to investigate whether race- and age-related differences in pediatric and adolescent and young adult (AYA) leukemia and lymphoma survival persist and to what extent these differences have changed over time. Using the Surveillance, Epidemiology, and End Results program, this study investigated the outcomes of black and white (1975-2012; n = 27,369) and white and Hispanic (1992-2012; n = 20,574) children (0-14 years old) and AYAs (15-39 years old) with acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), and Hodgkin lymphoma (HL). Estimates of 5- and 10-year relative survival were compared over time. Trends showed a convergence of survival for white and black children with ALL but a divergence in survival for AYA patients. Hispanic children and AYAs both suffered inferior outcomes. Trends for AML revealed persistent survival differences between black and white children and suggested worsening disparities for AYAs. Survival trends in HL revealed sustained survival differences between black and white AYA patients, whereas no differences were found in Hispanic and white patient outcomes for AML or HL. Although survival for children and AYAs with ALL, AML, and HL has improved over the past 4 decades, differences persist between black, white, and Hispanic children and AYAs; survival disparities between black and white children with ALL have been nearly eliminated. Strategies aimed at identifying causality and reducing disparities are warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2723-2730. © 2016 American Cancer Society. © 2016 American Cancer Society.

  20. The Incidence of Hypersensitivity Reactions to Pegylated Asparaginase in Children With Acute Lymphoblastic Leukemia: A City-wide Experience.

    Science.gov (United States)

    Alrazzak, Muaz; Beaupin, Lynda K; Kinyoun, Peter; Barth, Matthew

    2016-01-01

    Asparaginase (ASNase) is an imperative component of pediatric acute lymphoblastic leukemia (ALL) therapy. Pegylating the ASNase extends its biological half-life in vivo and has become the only ASNase available in the United States for frontline therapy of ALL and lymphoblastic lymphoma. It is either infused intravenously (IV) or injected intramuscularly (IM), administrations of which are associated with hypersensitivity reaction ranging from localized skin reaction to severe anaphylaxis. A retrospective review of 96 medical records of pediatric ALL patients was performed. We compared the incidence of hypersensitivity reaction associated with IV versus IM administration of pegylated ASNase. Ninety-one patients were included in the final analysis; 31 having received pegylated ASNase IV and 60 receiving it IM. The incidence of any grade ≥ 2 hypersensitivity reaction in patients who received IV ASNase was 32.2% compared with 13.3% in the IM group (P=0.032). There was no difference in higher grade hypersensitivity reactions (19.4% vs. 11.7%). Most reactions tended to occur during periods of leukemia therapy that did not include concomitant steroid therapy. Our retrospective analysis indicates that IV administration of pegylated ASNase increases the incidence of low-grade, but not grade 3-4, hypersensitivity reactions compared with IM administration.

  1. 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

  2. Targeted sequencing identifies associations between IL7R-JAK mutations and epigenetic modulators in T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    Vicente, Carmen; Schwab, Claire; Broux, Michaël; Geerdens, Ellen; Degryse, Sandrine; Demeyer, Sofie; Lahortiga, Idoya; Elliott, Alannah; Chilton, Lucy; La Starza, Roberta; Mecucci, Cristina; Vandenberghe, Peter; Goulden, Nicholas; Vora, Ajay; Moorman, Anthony V.; Soulier, Jean; Harrison, Christine J.; Clappier, Emmanuelle; Cools, Jan

    2015-01-01

    T-cell acute lymphoblastic leukemia is caused by the accumulation of multiple oncogenic lesions, including chromosomal rearrangements and mutations. To determine the frequency and co-occurrence of mutations in T-cell acute lymphoblastic leukemia, we performed targeted re-sequencing of 115 genes across 155 diagnostic samples (44 adult and 111 childhood cases). NOTCH1 and CDKN2A/B were mutated/deleted in more than half of the cases, while an additional 37 genes were mutated/deleted in 4% to 20% of cases. We found that IL7R-JAK pathway genes were mutated in 27.7% of cases, with JAK3 mutations being the most frequent event in this group. Copy number variations were also detected, including deletions of CREBBP or CTCF and duplication of MYB. FLT3 mutations were rare, but a novel extracellular mutation in FLT3 was detected and confirmed to be transforming. Furthermore, we identified complex patterns of pairwise associations, including a significant association between mutations in IL7R-JAK genes and epigenetic regulators (WT1, PRC2, PHF6). Our analyses showed that IL7R-JAK genetic lesions did not confer adverse prognosis in T-cell acute lymphoblastic leukemia cases enrolled in the UK ALL2003 trial. Overall, these results identify interconnections between the T-cell acute lymphoblastic leukemia genome and disease biology, and suggest a potential clinical application for JAK inhibitors in a significant proportion of patients with T-cell acute lymphoblastic leukemia. PMID:26206799

  3. Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group

    Science.gov (United States)

    Oriol, Albert; Vives, Susana; Hernández-Rivas, Jesús-María; Tormo, Mar; Heras, Inmaculada; Rivas, Concepción; Bethencourt, Concepción; Moscardó, Federico; Bueno, Javier; Grande, Carlos; del Potro, Eloy; Guardia, Ramon; Brunet, Salut; Bergua, Juan; Bernal, Teresa; Moreno, Maria-José; Calvo, Carlota; Bastida, Pilar; Feliu, Evarist; Ribera, Josep-Maria

    2010-01-01

    Background About one half of adults with acute lymphoblastic leukemia are not cured of the disease and ultimately die. The objective of this study was to explore the factors influencing the outcome of adult patients with relapsed acute lymphoblastic leukemia. Design and Methods We analyzed the characteristics, the outcome and the prognostic factors for survival after first relapse in a series of 263 adult patients with acute lymphoblastic leukemia (excluding those with mature B-cell acute lymphoblastic leukemia) prospectively enrolled in four consecutive risk-adapted PETHEMA trials. Results The median overall survival after relapse was 4.5 months (95% CI, 4–5 months) with a 5-year overall survival of 10% (95% CI, 8%–12%); 45% of patients receiving intensive second-line treatment achieved a second complete remission and 22% (95% CI, 14%–30%) of them remained disease free at 5 years. Factors predicting a good outcome after rescue therapy were age less than 30 years (2-year overall survival of 21% versus 10% for those over 30 years old; P<0.022) and a first remission lasting more than 2 years (2-year overall survival of 36% versus 17% among those with a shorter first remission; P<0.001). Patients under 30 years old whose first complete remission lasted longer than 2 years had a 5-year overall survival of 38% (95% CI, 23%–53%) and a 5-year disease-free survival of 53% (95% CI, 34%–72%). Conclusions The prognosis of adult patients with acute lymphoblastic leukemia who relapse is poor. Those aged less than 30 years with a first complete remission lasting longer than 2 years have reasonable possibilities of becoming long-term survivors while patients over this age or those who relapse early cannot be successfully rescued using the therapies currently available. PMID:20145276

  4. ATF5 polymorphisms influence ATF function and response to treatment in children with childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Rousseau, Julie; Gagné, Vincent; Labuda, Malgorzata; Beaubois, Cyrielle; Sinnett, Daniel; Laverdière, Caroline; Moghrabi, Albert; Sallan, Stephen E; Silverman, Lewis B; Neuberg, Donna; Kutok, Jeffery L; Krajinovic, Maja

    2011-11-24

    Asparaginase is a standard and critical component in the therapy of childhood acute lymphoblastic leukemia. Asparagine synthetase (ASNS) and the basic region leucine zipper activating transcription factor 5 (ATF5) and arginosuccinate synthase 1 (ASS1) have been shown to mediate the antileukemic effect of asparaginase and to display variable expression between leukemia cells that are resistant and sensitive to treatment. Fourteen polymorphisms in the regulatory and coding regions of these genes were investigated for an association with acute lymphoblastic leukemia outcome. Lower event-free survival (EFS) was associated with ATF5 T1562C, tandem-repeat ASNS polymorphism, derived haplotype, and ASS1 G1343T and G34T substitutions (P ≤ .03). Associations were limited to patients who received Escherichia coli asparaginase. Variations that sustained correction for multiple testing (ATF5 T1562C, P = .005; ASNS tandem-repeat and related haplotype, P ≤ .01) were subsequently analyzed in the replication cohort. The E coli-dependent association of the ATF5 T1562 allele with reduced EFS was confirmed (P = .01). A gene-reporter assay showed that the haplotype tagged by T1562 had higher promoter activity (P ≤ .01). The remaining regulatory polymorphisms also appeared to affect ATF5 function; 2 additional high-activity haplotypes were identified (P ≤ .02) and were further corroborated by quantitative mRNA analysis in lymphoblastoid cell lines. The ATF5-regulated increase in ASNS expression in response to more efficacious E coli-induced asparagine depletion may explain our observed results.

  5. Prognostic Significance of the Lymphoblastic Leukemia-Derived Sequence 1 (LYL1 Gene Expression in Egyptian Patients with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Nadia El Menshawy

    2014-06-01

    Full Text Available OBJECTIVE: Aberrant activation of transcription factor genes is the most frequent target of genetic alteration in lymphoid malignancies. The lymphoblastic leukemia-derived sequence 1 (LYL1 gene, which encodes a basic helix-loop helix, was first identified with human T-cell acute leukemia. Recent studies suggest its involvement in myeloid malignancies. We aimed to study the expression percent of oncogene LYL1 in primary and secondary high-risk myeloid leukemia and the impact on prognostic significance in those patients. METHODS: Using quantitative real-time polymerase chain reaction for detection of LYL1 oncogenes, our study was carried out on 39 myeloid leukemia patients including de novo cases, myelodysplastic syndrome (MDS with transformation, and chronic myelogenous leukemia (CML in accelerated and blast crisis, in addition to 10 healthy individuals as the reference control. RESULTS: LYL1 expression was increased at least 2 times compared to the controls. The highest expression of this transcription factor was observed in the MDS cases transformed to acute leukemia at 7.3±3.1, p=0.0011. LYL1 expression was found in 68.2%, 75%, and 77.8% of cases of acute myeloid leukemia, CML crisis, and MDS, respectively. Significant correlation of LYL1 overexpression with some subtypes of French-American-British classification was found. There was, for the first time, significant correlation between the blood count at diagnosis and LYL1 expression (p=0.023, 0.002, and 0.031 for white blood cells, hemoglobin, and platelets, respectively. The rate of complete remission was lower with very high levels of LYL1 expression and the risk of relapse increased with higher levels of LYL1 expression, suggesting an unfavorable prognosis for cases with enhanced expression. CONCLUSION: Overexpression of LYL1 is highly associated with acute myeloid leukemia and shows more expression in MDS with unfavorable prognosis in response to induction chemotherapy. These

  6. Gum hypertrophy--an unusual presenting feature in a case of precursor T-cell acute lymphoblastic leukemia/ Dis eti hipertrofisi ile giden bir prekursor T hucreli akut lenfoblastik losemi olgusu

    National Research Council Canada - National Science Library

    Premalata, Chennagiri Srinivasamurthy; Madhumathi, Davanam Satyanarayana; Lakshmidevi, Visweswraiah; Pradeep, Rudramurthy; Appaji, Lingappa; Mukherjee, Geetashree

    2008-01-01

    ... and the central nervous system. We present a rare case of precursor T-cell acute lymphoblastic leukemia/lymphoma with initial oral manifestation, presenting with the unusual features of gum hypertrophy and involvement of upper jaw...

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

    Science.gov (United States)

    2017-09-05

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

  8. CAR-T cells and allogeneic hematopoietic stem cell transplantation for relapsed/refractory B-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Liu, Jun; Zhang, Xi; Zhong, Jiang F; Zhang, Cheng

    2017-10-01

    Relapsed/refractory acute lymphoblastic leukemia (ALL) has a low remission rate after chemotherapy, a high relapse rate and poor long-term survival even when allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed. Chimeric antigen receptors redirected T cells (CAR-T cells) can enhance disease remission with a favorable outcome for relapsed/refractory ALL, though some cases quickly relapsed after CAR-T cell treatment. Thus, treatment with CAR-T cells followed by allo-HSCT may be the best way to treat relapsed/refractory ALL. In this review, we first discuss the different types of CAR-T cells. We then discuss the treatment of relapsed/refractory ALL using only CAR-T cells. Finally, we discuss the use of CAR-T cells, followed by allo-HSCT, for the treatment of relapsed/refractory ALL.

  9. Comparative efficacy of acute lymphoblastic leukemia treatment of children in St.-Petersburg using two COALL-92 versions

    Directory of Open Access Journals (Sweden)

    E. G. Boychenko

    2014-07-01

    Full Text Available Treatment results in children with acute lymphoblastic leukemia (ALL treating in St.-Petersburg hospitals according to two modified version of German protocol CO ALL-92 from 01.01.1993 to 01.01.2007 are presented. 438 primary A LL patients aged from 4 months to 17 year s have been included in the study . ALL diagnosed according to international criteria. Based on prognostic factors patients were a llocated to one of two risk groups, which determined therapy intensity . The total treatment duration in both groups w as 2 years and consist ed of 5.5–8 months intensive phase with subsequent maintenance therapy . A comparative treatment results analysis in children with A LL according to two modified versions of COALL-92 is presented.

  10. DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T-Cell Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Borssén, Magnus; Haider, Zahra; Landfors, Mattias

    2016-01-01

    BACKGROUND: Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects....... In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis and used for postinduction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T......-ALL. PROCEDURE: Sixty-five diagnostic T-ALL samples from Nordic pediatric patients treated according to the Nordic Society of Pediatric Hematology and Oncology ALL 2008 (NOPHO ALL 2008) protocol were analyzed by HumMeth450K genome wide DNA methylation arrays. Methylation status was analyzed in relation...

  11. DNA methylation as a potential mediator of environmental risks in the development of childhood acute lymphoblastic leukemia

    Science.gov (United States)

    Timms, Jessica A; Relton, Caroline L; Rankin, Judith; Strathdee, Gordon; McKay, Jill A

    2016-01-01

    5-year survival rate for childhood acute lymphoblastic leukemia (ALL) has risen to approximately 90%, yet the causal disease pathway is still poorly understood. Evidence suggests multiple ‘hits’ are required for disease progression; an initial genetic abnormality followed by additional secondary ‘hits’. It is plausible that environmental influences may trigger these secondary hits, and with the peak incidence of diagnosis between 2 and 5 years of age, early life exposures are likely to be key. DNA methylation can be modified by many environmental exposures and is dramatically altered in cancers, including childhood ALL. Here we explore the potential that DNA methylation may be involved in the causal pathway toward disease by acting as a mediator between established environmental factors and childhood ALL development. PMID:27035209

  12. Health-related quality of life of children on treatment for acute lymphoblastic leukemia: A systematic review.

    Science.gov (United States)

    Fardell, Joanna E; Vetsch, Janine; Trahair, T; Mateos, M K; Grootenhuis, M A; Touyz, L M; Marshall, G M; Wakefield, C E

    2017-09-01

    Children with acute lymphoblastic leukemia (ALL) undergo intense anticancer treatment. We systematically reviewed 22 studies evaluating 2,073 ALL patients' health-related quality of life (HRQL) and its clinical/demographic correlates during treatment. Overall HRQL was significantly reduced on treatment. Despite HRQL improvements over time, longitudinal studies reported a proportion of children continued to experience reduced HRQL after treatment completion. We found inconsistent associations between clinical/demographic factors and HRQL outcomes. Tentative evidence emerged for worse HRQL being associated with intensive phases of chemotherapy, corticosteroid therapy, experiencing greater toxicity, older age, and female sex. Longitudinal studies are needed to identify children at-risk of reduced HRQL. © 2017 Wiley Periodicals, Inc.

  13. DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T-Cell Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Borssén, Magnus; Haider, Zahra; Landfors, Mattias

    2016-01-01

    -ALL. PROCEDURE: Sixty-five diagnostic T-ALL samples from Nordic pediatric patients treated according to the Nordic Society of Pediatric Hematology and Oncology ALL 2008 (NOPHO ALL 2008) protocol were analyzed by HumMeth450K genome wide DNA methylation arrays. Methylation status was analyzed in relation......BACKGROUND: Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects....... In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis and used for postinduction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T...

  14. 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...

  15. Alterations in procoagulant, anticoagulant, and fibrinolytic systems before and after start of induction chemotherapy in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Albayrak, Meryem; Gürsel, Turkiz; Kaya, Zuhre; Koçak, Ulker

    2013-01-01

    Induction chemotherapy is associated with increased thrombosis risk in children with acute lymphoblastic leukemia (ALL). In this prospective study, we explored the effects of ALL and induction chemotherapy on the procoagulant, anticoagulant, and fibrinolytic systems in 20 children with ALL. The levels of d-dimer, factor VIII, von Willebrand factor, protein C, antithrombin III, and thrombin-activated fibrinolysis inhibitor (TAFI) were elevated at diagnosis. These changes were not related with peripheral blast count. The levels of fibrinogen, d-dimer, coagulation inhibitors, and plasminogen decreased, whereas the levels of tissue factor pathway inhibitor and plasminogen activator inhibitor 1 increased progressively following prednisolone monotherapy, administration of vincristine plus daunorubicin, and l-asparaginase. The levels of factor VIII, d-dimer, and TAFI remained elevated during the study period. In conclusion, coagulation activation and impaired fibrinolysis already exist at diagnosis, whereas induction chemotherapy leads to reactivation of coagulation and progressive impairment in fibrinolytic and anticoagulant capacities in childhood ALL.

  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...... 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)....... and has higher affinity and selectivity to the 5-HT(3) receptor. Adult studies have demonstrated that palonosetron is both more effective and require fewer administrations than first generation 5-HT(3) receptor antagonists. The purpose of this study was to examine the effect of a single dose...

  17. Systematic chemical and molecular profiling of MLL-rearranged infant acute lymphoblastic leukemia reveals efficacy of romidepsin

    Science.gov (United States)

    Cruickshank, M N; Ford, J; Cheung, L C; Heng, J; Singh, S; Wells, J; Failes, T W; Arndt, G M; Smithers, N; Prinjha, R K; Anderson, D; Carter, K W; Gout, A M; Lassmann, T; O'Reilly, J; Cole, C H; Kotecha, R S; Kees, U R

    2017-01-01

    To address the poor prognosis of mixed lineage leukemia (MLL)-rearranged infant acute lymphoblastic leukemia (iALL), we generated a panel of cell lines from primary patient samples and investigated cytotoxic responses to contemporary and novel Food and Drug Administration-approved chemotherapeutics. To characterize representation of primary disease within cell lines, molecular features were compared using RNA-sequencing and cytogenetics. High-throughput screening revealed variable efficacy of currently used drugs, however identified consistent efficacy of three novel drug classes: proteasome inhibitors, histone deacetylase inhibitors and cyclin-dependent kinase inhibitors. Gene expression of drug targets was highly reproducible comparing iALL cell lines to matched primary specimens. Histone deacetylase inhibitors, including romidepsin (ROM), enhanced the activity of a key component of iALL therapy, cytarabine (ARAC) in vitro and combined administration of ROM and ARAC to xenografted mice further reduced leukemia burden. Molecular studies showed that ROM reduces expression of cytidine deaminase, an enzyme involved in ARAC deactivation, and enhances the DNA damage–response to ARAC. In conclusion, we present a valuable resource for drug discovery, including the first systematic analysis of transcriptome reproducibility in vitro, and have identified ROM as a promising therapeutic for MLL-rearranged iALL. PMID:27443263

  18. Modeling the evolution of ETV6-RUNX1-induced B-cell precursor acute lymphoblastic leukemia in mice.

    Science.gov (United States)

    van der Weyden, Louise; Giotopoulos, George; Rust, Alistair G; Matheson, Louise S; van Delft, Frederik W; Kong, Jun; Corcoran, Anne E; Greaves, Mel F; Mullighan, Charles G; Huntly, Brian J; Adams, David J

    2011-07-28

    The t(12;21) translocation that generates the ETV6-RUNX1 (TEL-AML1) fusion gene, is the most common chromosomal rearrangement in childhood cancer and is exclusively associated with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The translocation arises in utero and is necessary but insufficient for the development of leukemia. Single-nucleotide polymorphism array analysis of ETV6-RUNX1 patient samples has identified multiple additional genetic alterations; however, the role of these lesions in leukemogenesis remains undetermined. Moreover, murine models of ETV6-RUNX1 ALL that faithfully recapitulate the human disease are lacking. To identify novel genes that cooperate with ETV6-RUNX1 in leukemogenesis, we generated a mouse model that uses the endogenous Etv6 locus to coexpress the Etv6-RUNX1 fusion and Sleeping Beauty transposase. An insertional mutagenesis screen was performed by intercrossing these mice with those carrying a Sleeping Beauty transposon array. In contrast to previous models, a substantial proportion (20%) of the offspring developed BCP-ALL. Isolation of the transposon insertion sites identified genes known to be associated with BCP-ALL, including Ebf1 and Epor, in addition to other novel candidates. This is the first mouse model of ETV6-RUNX1 to develop BCP-ALL and provides important insight into the cooperating genetic alterations in ETV6-RUNX1 leukemia.

  19. Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Etienne Danis

    2016-03-01

    Full Text Available Early T cell precursor acute lymphoblastic leukemia (ETP-ALL is an aggressive subtype of ALL distinguished by stem-cell-associated and myeloid transcriptional programs. Inactivating alterations of Polycomb repressive complex 2 components are frequent in human ETP-ALL, but their functional role is largely undefined. We have studied the involvement of Ezh2 in a murine model of NRASQ61K-driven leukemia that recapitulates phenotypic and transcriptional features of ETP-ALL. Homozygous inactivation of Ezh2 cooperated with oncogenic NRASQ61K to accelerate leukemia onset. Inactivation of Ezh2 accentuated expression of genes highly expressed in human ETP-ALL and in normal murine early thymic progenitors. Moreover, we found that Ezh2 contributes to the silencing of stem-cell- and early-progenitor-cell-associated genes. Loss of Ezh2 also resulted in increased activation of STAT3 by tyrosine 705 phosphorylation. Our data mechanistically link Ezh2 inactivation to stem-cell-associated transcriptional programs and increased growth/survival signaling, features that convey an adverse prognosis in patients.

  20. Combination therapeutics of Nilotinib and radiation in acute lymphoblastic leukemia as an effective method against drug-resistance.

    Directory of Open Access Journals (Sweden)

    Kamran Kaveh

    2017-07-01

    Full Text Available Philadelphia chromosome-positive (Ph+ acute lymphoblastic leukemia (ALL is characterized by a very poor prognosis and a high likelihood of acquired chemo-resistance. Although tyrosine kinase inhibitor (TKI therapy has improved clinical outcome, most ALL patients relapse following treatment with TKI due to the development of resistance. We developed an in vitro model of Nilotinib-resistant Ph+ leukemia cells to investigate whether low dose radiation (LDR in combination with TKI therapy overcome chemo-resistance. Additionally, we developed a mathematical model, parameterized by cell viability experiments under Nilotinib treatment and LDR, to explain the cellular response to combination therapy. The addition of LDR significantly reduced drug resistance both in vitro and in computational model. Decreased expression level of phosphorylated AKT suggests that the combination treatment plays an important role in overcoming resistance through the AKT pathway. Model-predicted cellular responses to the combined therapy provide good agreement with experimental results. Augmentation of LDR and Nilotinib therapy seems to be beneficial to control Ph+ leukemia resistance and the quantitative model can determine optimal dosing schedule to enhance the effectiveness of the combination therapy.