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Sample records for relapsed childhood acute

  1. 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...

  2. Treatment-related mortality in relapsed childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

    2018-01-01

    BACKGROUND: Treatment of relapsed childhood acute lymphoblastic leukemia (ALL) is particularly challenging due to the high treatment intensity needed to induce and sustain a second remission. To improve results, it is important to understand how treatment-related toxicity impacts survival...

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

    International Nuclear Information System (INIS)

    Chessells, J.; Leiper, A.; Rogers, D.

    1984-01-01

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

  4. Treatment of relapsed or refractory acute leukemia in childhood with bisantrene combined with high dose aracytine.

    Science.gov (United States)

    Leblanc, T; Deméocq, F; Leverger, G; Baruchel, A; Lemerle, S; Vannier, J P; Nelken, B; Guillot, T; Schaison, G

    1994-01-01

    Bisantrene is an anthracene derivative which has demonstrated activity in acute myeloblastic leukemia (AML) and in lymphoma. The present study was designed to assess the reinduction rate and toxicity of bisantrene (250 mg/m2/d x 5) associated with aracytine (100 mg/m2 twice a day x 5) in refractory and relapsed acute childhood leukemia. Patients who relapsed after bone marrow transplantation were eligible. Twenty-six children were included. Diagnoses were as follows: 13 AML, 9 acute lymphoblastic leukemia (ALL), and 4 undifferentiated leukemia (AUL). All patients had been very highly pretreated, especially with anthracyclines, and most of them were of poor prognosis. The overall response rate was 46% with a 95% confidence interval ranging from 27-65%. According to diagnosis, complete remission (CR) rates are: AML: 5/13, ALL: 5/9, and AUL: 2/4. Four children died, three from infection and one from acute lysis syndrome. The major toxicity was infection with grade 3 and 4 episodes occurring in 42% of patients. No significant cardiac toxicity was noted. Hepatic and renal toxicity was noted. Hepatic and renal toxicity were limited and transient. Bisantrene in association with aracytine is effective in both AML and ALL of childhood. Bisantrene should be evaluated with a five-day schedule in other pediatric malignancies. In children with acute leukemia previously treated with high dose aracytine, new combination regimen is warranted.

  5. 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...

  6. Relapsed childhood high hyperdiploid acute lymphoblastic leukemia: presence of preleukemic ancestral clones and the secondary nature of microdeletions and RTK-RAS mutations

    DEFF Research Database (Denmark)

    Davidsson, J; Paulsson, K; Lindgren, D

    2010-01-01

    Although childhood high hyperdiploid acute lymphoblastic leukemia is associated with a favorable outcome, 20% of patients still relapse. It is important to identify these patients already at diagnosis to ensure proper risk stratification. We have investigated 11 paired diagnostic and relapse samp...

  7. Relapsed childhood high hyperdiploid acute lymphoblastic leukemia: presence of preleukemic ancestral clones and the secondary nature of microdeletions and RTK-RAS mutations

    DEFF Research Database (Denmark)

    Davidsson, J; Paulsson, K; Lindgren, D

    2010-01-01

    Although childhood high hyperdiploid acute lymphoblastic leukemia is associated with a favorable outcome, 20% of patients still relapse. It is important to identify these patients already at diagnosis to ensure proper risk stratification. We have investigated 11 paired diagnostic and relapse...

  8. 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

  9. 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)

    Berg, H. van den; Groot-Kruseman, H.A. de; Damen-Korbijn, C.M.; Bont, E.S. de; Schouten-van Meeteren, A.Y.; Hoogerbrugge, P.M.

    2011-01-01

    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

  10. 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.

    2011-01-01

    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

  11. Genomic profiling of thousands of candidate polymorphisms predicts risk of relapse in 778 Danish and German childhood acute lymphoblastic leukemia patients

    DEFF Research Database (Denmark)

    Wesolowska, Agata; Borst, L.; Dalgaard, Marlene Danner

    2015-01-01

    Childhood acute lymphoblastic leukemia survival approaches 90%. New strategies are needed to identify the 10–15% who evade cure. We applied targeted, sequencing-based genotyping of 25 000 to 34 000 preselected potentially clinically relevant singlenucleotide polymorphisms (SNPs) to identify host...... associated with risk of relapse across protocols. SNP and biologic pathway level analyses associated relapse risk with leukemia aggressiveness, glucocorticosteroid pharmacology/response and drug transport/metabolism pathways. Classification and regression tree analysis identified three distinct risk groups...... defined by end of induction residual leukemia, white blood cell count and variants in myeloperoxidase (MPO), estrogen receptor 1 (ESR1), lamin B1 (LMNB1) and matrix metalloproteinase-7 (MMP7) genes, ATP-binding cassette transporters and glucocorticosteroid transcription regulation pathways. Relapse rates...

  12. Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Irving, J.A.; Enshaei, A.; Parker, C.A.; Sutton, R.; Kuiper, R.P.; Erhorn, A.; Minto, L.; Venn, N.C.; Law, T.; Yu, J.; Schwab, C.; Davies, R.; Matheson, E.; Davies, A.; Sonneveld, E.; Boer, M.L. Den; Love, S.B.; Harrison, C.J.; Hoogerbrugge, P.M.; Revesz, T.; Saha, V.; Moorman, A.V.

    2016-01-01

    Somatic genetic abnormalities are initiators and drivers of disease and have proven clinical utility at initial diagnosis. However, the genetic landscape and its clinical utility at relapse are less well understood and have not been studied comprehensively. We analyzed cytogenetic data from 427

  13. Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukemia

    NARCIS (Netherlands)

    J. Irving (Julie); A. Enshaei; Parker, C.A. (Catriona A.); R. Sutton; R. Kuiper (Ruud); Erhorn, A. (Amy); L. Minto (L.); N. Venn; T. Law (T.); Yu, J. (Jiangyan); C. Schwab (Claire); Davies, R. (Rosanna); Matheson, E. (Elizabeth); Davies, A. (Alysia); E. Sonneveld (Edwin); M.L. den Boer (Monique); Love, S.B. (Sharon B.); C.J. Harrison (Christine); P.M. Hoogerbrugge (Peter); T. Revesz (Tamas); V. Saha (Vaskar); A.V. Moorman (Anthony)

    2016-01-01

    textabstractSomatic genetic abnormalities are initiators and drivers of disease and have proven clinical utility at initial diagnosis. However, the genetic landscape and its clinical utility at relapse are less well understood and have not been studied comprehensively. We analyzed cytogenetic data

  14. TBI parameters and relapse of acute leukemia

    International Nuclear Information System (INIS)

    Sugawara, Tadashi; Inoue, Toshihiko; Mori, Tomoyuki.

    1994-01-01

    The purpose of this study, which involved 240 acute leukemia patients (ALL: 115, ANL: 125) who received an allogeneic bone marrow transplantation (BMT) with preconditioning by total body irradiation (TBI) and chemotherapy, was to examine retrospectively the TBI factors that may have influenced a leukemic relapse. The patients were divided into two groups: 124 patients who had received their BMT within a diagnosis-transplantation period of 9 months or less (DTP9 group), and 116 patients who had received their BMT within a diagnosis-transplantation period of 10 months or more (DTP10 group). It was concluded that: (1) the higher the TBI dose, the fewer the relapse rates in DTP9 group; (2) the longer the TBI period, the greater the increase in the relapse rate in DTP10 group. It was thus speculated that an effective TBI regimen for acute leukemia patients may vary depending on the length of time that has elapsed from the diagnosis of leukemia to the BMT. (author)

  15. 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...

  16. 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.

  17. DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial.

    Science.gov (United States)

    Nielsen, Stine Nygaard; Grell, Kathrine; Nersting, Jacob; Abrahamsson, Jonas; Lund, Bendik; Kanerva, Jukka; Jónsson, Ólafur Gísli; Vaitkeviciene, Goda; Pruunsild, Kaie; Hjalgrim, Lisa Lyngsie; Schmiegelow, Kjeld

    2017-04-01

    Adjustment of mercaptopurine and methotrexate maintenance therapy of acute lymphoblastic leukaemia by leucocyte count is confounded by natural variations. Cytotoxicity is primarily mediated by DNA-incorporated thioguanine nucleotides (DNA-TGN). The aim of this study was to establish whether DNA-TGN concentrations in blood leucocytes during maintenance therapy are associated with relapse-free survival. In this substudy of the NOPHO ALL2008 phase 3 trial done in 23 hospitals in seven European countries (Denmark, Estonia, Finland, Iceland, Lithuania, Norway, and Sweden), we analysed data from centralised and blinded analyses of 6-mercaptopurine and methotrexate metabolites in blood samples from patients with non-high-risk childhood acute lymphoblastic leukaemia. Eligible patients were aged 1·0-17·9 years; had been diagnosed with non-high-risk precursor B-cell or T-cell leukaemia; had been treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol; and had reached maintenance therapy in first remission. Maintenance therapy was (mercaptopurine 75 mg/m 2 once per day and methotrexate 20 mg/m 2 once per week, targeted to a leucocyte count of 1·5-3·0 × 10 9 cells per L). We measured DNA-TGN and erythrocyte concentrations of TGN nucleotides, methylated mercaptopurine metabolites, and methotrexate polyglutamates. The primary objective was the association of DNA-TGN concentrations and 6-mercaptopurine and methotrexate metabolites with relapse-free survival. The secondary endpoint was the assessment of DNA-TGN concentration and 6-mercaptopurine and methotrexate metabolites during maintenance therapy phase 2. Between Nov 26, 2008 and June 14, 2016, 1509 patients from the NOPHO ALL2008 study were assessed for eligibility in the DNA-TGN substudy, of which 918 (89%) of 1026 eligible patients had at least one DNA-TGN measurement and were included in the analyses. Median follow-up was 4·6 years (IQR 3·1-6·1). Relapse-free survival was

  18. Acute hemiplegia in childhood

    International Nuclear Information System (INIS)

    Okuno, Takehiko; Takao, Tatsuo; Itoh, Masatoshi; Konishi, Yukuo; Nakano, Shozo

    1983-01-01

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

  19. Prolonged persistence of PCR-detectable minimal residual disease after diagnosis or first relapse predicts poor outcome in childhood B-precursor acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Steenbergen, E. J.; Verhagen, O. J.; van Leeuwen, E. F.; van den Berg, H.; Behrendt, H.; Slater, R. M.; von dem Borne, A. E.; van der Schoot, C. E.

    1995-01-01

    The follow up of minimal residual disease (MRD) in childhood B-precursor ALL by polymerase chain reaction (PCR) may be of help for further stratification of treatment protocols, to improve outcome. However, the clinical relevance of this approach has yet to be defined. We report the retrospective

  20. Benign acute childhood myositis.

    Science.gov (United States)

    Rajajee, Sarala; Ezhilarasi, S; Rajarajan, K

    2005-05-01

    To describe the clinical and laboratory features of benign acute childhood myositis. 40 children of BACM were seen during October 2001 to February 2002, 22 (52%) were male with mean age of 5.3 years. Duration of illness was 3.97 days. Preceding symptoms included fever, leg pain, vomiting and inability to walk. A provisional diagnosis of viral myositis was made in 26 (66%). Guillian Barre Syndrome was the most common referral diagnosis. 11 (27.5%) children had leucopenia with lymphocytic response and 16 (40%) had thrombocytopenia. CRP was negative in 32 (80%). CPK was markedly elevated (more than 1000 IU/l) in 18 (45%) and more than 500 IU/l in 11 (27.5%) remaining between 200 to 500 IU/l. Associated features were hepatitis (elevated SGOT & SGPT) in 28 (70%) and shock in 5 (12.5%). Serological test were indicative of dengue virus (Elisa PAN BIO) in 20 (50%) of which 8 (25%) were primary dengue and 12 (30%) were secondary dengue. The outcome of therapy mainly supportive were excellent. Benign acute myositis occurs often in association with viral infection. In the present study, Dengue virus was positive in 20 (50%) children. Benign acute myositis can be differentiated from more serious causes of walking difficulty by presence of calf and thigh muscle tenderness on stretching, normal power and deep tendon reflex and elevated CPK.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    BACKGROUND: Adjustment of mercaptopurine and methotrexate maintenance therapy of acute lymphoblastic leukaemia by leucocyte count is confounded by natural variations. Cytotoxicity is primarily mediated by DNA-incorporated thioguanine nucleotides (DNA-TGN). The aim of this study was to establish w...

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

    DEFF Research Database (Denmark)

    Abrahamsson, Jonas; Clausen, Niels; Gustafsson, Göran

    2007-01-01

    investigated. The study included all 146 children in the Nordic countries diagnosed with AML between 1988 and 2003, who relapsed. Data on disease characteristics and relapse treatment were related to outcome. Sixty-six percentage achieved remission with survival after relapse (5 years) 34 +/- 4%. Of 122......In the Nordic Society for Paediatric Haematology and Oncology paediatric study acute myeloid leukaemia (AML) 93, event-free survival was 50% and overall survival was 66%, indicating that many patients were cured following relapse. Factors influencing outcome in children with relapsed AML were...... patients who received re-induction therapy, 77% entered remission with 40 +/- 5% survival. Remission rates were similar for different re-induction regimens but fludarabine, cytarabine, granulocyte colony-stimulating factor-based therapy had low treatment-related mortality. Prognostic factors for survival...

  3. A Unique Case of Relapsing Polychondritis Presenting with Acute Pericarditis

    Directory of Open Access Journals (Sweden)

    John V. Higgins

    2013-01-01

    Full Text Available Relapsing polychondritis (RP is an inflammatory disease of the cartilaginous tissue primarily affecting the cartilaginous structures of the ear, nose, joints, and the respiratory system. Cardiovascular complications of RP are associated with high morbidity and mortality and occur most commonly as valvular disease. Pericarditis is a less common complication, occurring in 4% of patients with RP and has not previously been described at presentation. We describe a case of relapsing polychondritis with acute pericarditis at presentation.

  4. 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

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

    Science.gov (United States)

    2018-02-28

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

  6. 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......-MTX (pharmacology group), or by WBC only (control group). RESULTS: After a median follow-up of 7.8 years, 79 patients had relapsed. Cox regression analysis showed an increased risk of relapse for boys (P =.00003), high WBC at diagnosis (P =.03), pharmacology arm (6.6 times increased relapse hazard for girls), high...

  7. Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML

    Science.gov (United States)

    2018-03-05

    Relapsed Acute Lymphoblastic Leukemia (ALL); Refractory Acute Lymphoblastic Leukemia (ALL); Relapsed Acute Myelogenous Leukemia (AML); Refractory Acute Myelogenous Leukemia (AML); Relapsed Mixed Lineage Leukemia; Refractory Mixed Lineage Leukemia; Relapsed Biphenotypic Leukemia; Refractory Biphenotypic Leukemia; Chronic Myelogenous Leukemia (CML) in Blast Crisis

  8. Side effects of treatment in childhood acute leukemia, 2

    International Nuclear Information System (INIS)

    Fujinami, Akira; Murakami, Mako; Sako, Masahiro; Takubo, Yoshiyuki; Nakagawa, Kimiko; Konishi, Shouzaburo; Tsujino, Giiti; Hata, Shinn; Koizumi, Yoshiko

    1989-01-01

    We evaluated delayed neurotoxicities in treatment of childhood acute leukemia. Of 28 patients treated over 2 years who were examined on computed tomography of brain scans, 7 patients had abnormal findings. These abnormalities included two cases of leukoencephalopathy, three cases of intracranial calcifications, and two of ventricular dilatation. These patients were under 6 years old at the onset of disease, especially under 3 years old. Also, delayed neurotoxicities developed after relapse of leukemia, especially CNS relapse. It was considered that these were caused by cranial irradiation, intravenous methotrexate injection, intrathecal methotrexate, and sometimes high-dose Ara-C therapy, etc. Most of the cases of leukoencephalopathy were associated with treatment of intermediate-dose or high-dose methotrexate after relapse. These abnormalities must be carefully considered in the treatment of younger children with leukemia and patients with relapse. (author)

  9. Temporal changes in incidence and pattern of central nervous system relapses in children with acute lymphoblastic leukaemia treated on four consecutive Medical Research Council Trials, 1985–2001

    Science.gov (United States)

    Krishnan, Shekhar; Wade, Rachel; Moorman, Anthony V; Mitchell, Chris; Kinsey, Sally E; Eden, TOB; Parker, Catriona; Vora, Ajay; Richards, Sue; Saha, Vaskar

    2009-01-01

    Despite the success of contemporary treatment protocols in childhood acute lymphoblastic leukaemia (ALL), relapse within the central nervous system (CNS) remains a challenge. To better understand this phenomenon, we have analysed the changes in incidence and pattern of CNS relapses in 5564 children enrolled on four successive MRC-ALL trials between 1985 and 2001. Changes in the incidence and pattern of CNS relapses were examined and the relationship with patient characteristics assessed. Factors affecting post-relapse outcome were determined. Overall, relapses declined by 49%. Decreases occurred primarily in non-CNS and combined relapses with a progressive shift towards later (≥30 months from diagnosis) relapses (p<0·0001). Although isolated CNS relapses declined, the proportional incidence and timing of relapse remained unchanged. Age and presenting white cell count were risk factors for CNS relapse. On multivariate analysis, the time to relapse and the trial period influenced post-relapse outcomes. Relapse trends differed within biological subtypes. In ETV6-RUNX1 ALL, relapse patterns mirrored overall trends while in High Hyperdiploidy ALL, these appear to have plateaued over the latter two trial periods. Intensive systemic and intrathecal chemotherapy have decreased the overall CNS relapse rates and changed the patterns of recurrence. The heterogeneity of therapeutic response in the biological subtypes suggests room for further optimisation using currently available chemotherapy. PMID:20016529

  10. Acute severe childhood asthma

    African Journals Online (AJOL)

    Attending school regularly. • Sleeping well at night ... and children must know exactly what to do when an acute attack occurs, and when to ... peak flow reading that is 30% below the expected level, are ... oxygen saturations < 94%, should receive high-flow oxygen ... usual of the metered dose inhaler are required to achieve.

  11. Acute leukemia in early childhood

    Directory of Open Access Journals (Sweden)

    M. Emerenciano

    2007-06-01

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

  12. Acute childhood leukemia: Nursing care

    International Nuclear Information System (INIS)

    Zietz, Hallie A

    1997-01-01

    Modern therapy for childhood acute leukemia has provided a dramatically improved prognosis over that of just 30 years ago. In the early 1960's survival rates for acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML) were 4% and 3%, respectively. By the 1980's survival rates had risen to 72% for all and 25% to 40% for AML. Today, a diagnosis of all carries an 80% survival rate and as high as a 90% survival rate for some low-risk subtypes. Such high cure rates depend on intense and complex, multimodal therapeutic protocols. Therefore, nursing care of the child with acute leukemia must meet the demands of complicated medical therapies and balance those with the needs of a sick child and their concerned family. An understanding of disease process and principles of medical management guide appropriate and effective nursing interventions. Leukemia is a malignant disorder of the blood and blood- forming organs (bone marrow, lymph nodes and spleen). Most believe that acute leukemia results from a malignant transformation of a single early haematopoietic stem cell that is capable of indefinite self-renewal. These immature cells of blasts do not respond to normal physiologic stimuli for differentiation and gradually become the predominant cell in the bone marrow

  13. 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

  14. Global Characteristics of Childhood Acute Promyelocytic Leukemia

    Science.gov (United States)

    Zhang, L; Samad, A; Pombo-de-Oliveira, MS; Scelo, G; Smith, MT; Feusner, J; Wiemels, JL; Metayer, C

    2014-01-01

    Acute promyelocytic leukemia (APL) comprises approximately 5–10% of childhood acute myeloid leukemia (AML) cases in the US. While variation in this percentage among other populations was noted previously, global patterns of childhood APL have not been thoroughly characterized. In this comprehensive review of childhood APL, we examined its geographic pattern and the potential contribution of environmental factors to observed variation. In 142 studies (spanning >60 countries) identified, variation was apparent—de novo APL represented from 2% (Switzerland) to >50% (Nicaragua) of childhood AML in different geographic regions. Because a limited number of previous studies addressed specific environmental exposures that potentially underlie childhood APL development, we gathered 28 childhood cases of therapy-related APL, which exemplified associations between prior exposures to chemotherapeutic drugs/radiation and APL diagnosis. Future population-based studies examining childhood APL patterns and the potential association with specific environmental exposures and other risk factors are needed. PMID:25445717

  15. Relapsed Acute Promyelocytic Leukemia Lacks "Classic" Leukemic Promyelocyte Morphology and Can Create Diagnostic Challenges.

    Science.gov (United States)

    Dayton, Vanessa J; McKenna, Robert W; Yohe, Sophia L; Dolan, Michelle M; Courville, Elizabeth; Alvarez, Harold; Linden, Michael A

    2017-01-01

    Although current therapies for acute promyelocytic leukemia (APL), such as all- trans retinoic acid and arsenic trioxide, usually result in remission, some patients relapse. Early recognition of relapse is critical for prompt intervention. In this study, we systematically reviewed morphologic, immunophenotypic, and cytogenetic findings in paired diagnostic and relapsed APL cases and describe and quantify the changes in blast morphology at relapse. By electronic database search, we identified eight paired diagnostic and relapsed APL cases for which peripheral blood or bone marrow smears were available for review. For two cases, diagnostic material was available for relapse after hematopoietic cell transplantation. Neoplastic hypergranular or microgranular promyelocytes with indented or bivalve nuclei predominated at diagnosis in all patients. Most patients had undifferentiated blasts at relapse and/or hypergranular blast equivalents with round to oval nuclei. Classic acute promyelocytic leukemia cells with bivalve nuclei and bundles of cytoplasmic Auer rods were easily identifiable in fewer than half of cases at diagnosis and rare to absent in all relapsed cases. Morphologic features of relapsed APL overlap with other types of acute myeloid leukemia, creating diagnostic challenges, especially if no history is available when relapsing patients seek treatment for care. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  16. Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome

    NARCIS (Netherlands)

    Teeninga, N.; Kist-van Holthe, J.E.; Rijswijk, N. van; Mos, N.I. de; Hop, W.C.J.; Wetzels, J.F.M.; Heijden, A.J. van der; Nauta, J.

    2013-01-01

    Prolonged prednisolone treatment for the initial episode of childhood nephrotic syndrome may reduce relapse rate, but whether this results from the increased duration of treatment or a higher cumulative dose remains unclear. We conducted a randomized, double-blind, placebo-controlled trial in 69

  17. Targeting FLT3 Signaling in Childhood Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Amy N. Sexauer

    2017-11-01

    Full Text Available Acute myeloid leukemia (AML is the second most common leukemia of childhood and is associated with high rates of chemotherapy resistance and relapse. Clinical outcomes for children with AML treated with maximally intensive multi-agent chemotherapy lag far behind those of children with the more common acute lymphoblastic leukemia, demonstrating continued need for new therapeutic approaches to decrease relapse risk and improve long-term survival. Mutations in the FMS-like tyrosine kinase-3 receptor gene (FLT3 occur in approximately 25% of children and adults with AML and are associated with particularly poor prognoses. Identification and development of targeted FLT3 inhibitors represents a major precision medicine paradigm shift in the treatment of patients with AML. While further development of many first-generation FLT3 inhibitors was hampered by limited potency and significant toxicity due to effects upon other kinases, the more selective second- and third-generation FLT3 inhibitors have demonstrated excellent tolerability and remarkable efficacy in the relapsed/refractory and now de novo FLT3-mutated AML settings. While these newest and most promising inhibitors have largely been studied in the adult population, pediatric investigation of FLT3 inhibitors with chemotherapy is relatively recently ongoing or planned. Successful development of FLT3 inhibitor-based therapies will be essential to improve outcomes in children with this high-risk subtype of AML.

  18. [Clinical and biological prognostic factors in relapsed acute myeloid leukemia patients].

    Science.gov (United States)

    Yébenes-Ramírez, Manuel; Serrano, Josefina; Martínez-Losada, Carmen; Sánchez-García, Joaquín

    2016-09-02

    Acute myeloid leukemia (AML) is the most frequent type of acute leukemia in adults. Despite recent advances in the characterization of pathogenesis of AML, the cure rates are under 40%, being leukemia relapse the most common cause of treatment failure. Leukaemia relapse occurs due to clonal evolution or clonal escape. In this study, we aimed to analyze the clinical and biological factors influencing outcomes in patients with AML relapse. We included a total of 75 AML patients who experienced leukaemia relapse after achieving complete remission. We performed complete immunophenotyping and conventional karyotyping in bone marrow aspirates obtained at diagnosis and at leukemia relapse. Overall survival (OS) of the series was 3.7%±2.3, leukaemia progression being the most common cause of death. Patients relapsing before 12 months and those with adverse cytogenetic-molecular risk had statistically significant worse outcomes. A percentage of 52.5 of patients showed phenotypic changes and 50% cytogenetic changes at relapse. We did not find significant clinical factors predicting clonal evolution. The presence of clonal evolution at relapse did not have a significant impact on outcome. Patients with relapsed AML have a dismal prognosis, especially those with early relapse and adverse cytogenetic-molecular risk. Clonal evolution with phenotypic and cytogenetic changes occurred in half of the patients without predictive clinical factors or impact on outcome. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  19. Molecular discrimination between relapsed and secondary acute lymphoblastic leukemia : Proposal for an easy strategy

    NARCIS (Netherlands)

    Szczepanski, T; Willemse, MJ; Kamps, WA; van Wering, ER; Langerak, AW; van Dongen, JJM

    Background. Discrimination between late relapse of acute lymphoblastic leukemia (ALL) and secondary ALL might be clinically important, because the former might still respond favorably to chemotherapy and/or bone marrow transplantation, whereas secondary ALL is associated with poor prognosis.

  20. Isolated Extramedullary Relapse of Acute Leukemia after Allogeneic Stem Cell Transplantation: Different Kinetics and Better Prognosis than Systemic Relapse.

    Science.gov (United States)

    Shem-Tov, Noga; Saraceni, Francesco; Danylesko, Ivetta; Shouval, Roni; Yerushalmi, Ronit; Nagler, Arnon; Shimoni, Avichai

    2017-07-01

    Allogeneic stem cell transplantation (SCT) is curative treatment in patients with acute leukemia and myelodysplastic syndrome. However, recurrent disease is the major cause of treatment failure. Isolated extramedullary relapse (iEMR) after SCT is relatively rare and not well characterized. We performed a retrospective analysis of 566 consecutive patients with acute myeloid leukemia (n = 446) and acute lymphoblastic leukemia (ALL; n = 120) after SCT to study the incidence, risk factors, treatment options, and outcome of iEMR. The 5-year cumulative incidence of bone marrow relapse (BMR) and iEMR was 41.0% and 5.8%, respectively. iEMR occurred significantly later than BMR at 10 and 4 months, respectively (P BMR but did not protect against iEMR. Most patients with iEMR received systemic treatment combined with local radiation and donor lymphocyte infusions when feasible. The 3-year survival after relapse was 8.5% and 30.1% after BMR and iEMR, respectively (P = .002). Patients with a first iEMR continued to have recurrent EMRs, and only a minority progressed to BMR. Second iEMR was also common after first BMR and associated with longer survival than second BMR. iEMR is more frequent in patients with ALL and prior extramedullary disease. It occurs later than BMR and more commonly in patients with chronic GVHD, suggesting less effective graft-versus-leukemia effect in extramedullary sites. Second iEMR is common after a first iEMR but also after a first BMR. Long-term survival is feasible with aggressive treatment. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  1. Leukemic blasts are present at low levels in spinal fluid in one-third of childhood acute lymphoblastic leukemia cases

    DEFF Research Database (Denmark)

    Levinsen, Mette; Marquart, Hanne V; Groth-Pedersen, Line

    2016-01-01

    BACKGROUND: Central nervous system (CNS) involvement is associated with relapse in childhood acute lymphoblastic leukemia (ALL) and is a diagnostic challenge. PROCEDURE: In a Nordic/Baltic prospective study, we assessed centralized flow cytometry (FCM) of locally fixed cerebrospinal fluid (CSF......: 45 × 10(9) /l vs. 10 × 10(9) /l, P diagnosis remained so despite at least two doses...

  2. 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)

    2018-04-30

    HLA-A*0201 HA-1 Positive Cells Present; Minimal Residual Disease; Recurrent Acute Biphenotypic Leukemia; Recurrent Acute Undifferentiated Leukemia; 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

  3. Relapse after methylprednisolone oral minipulse therapy in childhood vitiligo: A 12-month follow-up study

    Directory of Open Access Journals (Sweden)

    Imran Majid

    2013-01-01

    Full Text Available Background: Oral minipulse (OMP therapy with methylprednisolone is presently one of the most common oral treatments used for progressive vitiligo in children. The treatment is usually given for a period of 6 months during which majority of patients are reported to go into remission. However, there are no follow-up studies to comment upon what happens to the disease after OMP therapy is withdrawn. Aim of the study: To document the incidence of relapse over a period of 1 year after OMP therapy is stopped in children with vitiligo. Materials and Methods: The study was conducted in 180 patients of childhood vitiligo (<15 years of age who had been on OMP therapy with oral methylprednisolone for at least 6 months and who had achieved a complete remission of their disease during the treatment period. The enrolled patients were followed up for a period of 1 year and examined clinically for any sign of reactivation of their disease over either the old lesions or at any new area of the body. Results: Forty-two patients were lost and could not complete the follow-up period of 1 year. Out of the 138 patients available at the end of 1 year, relapse was observed in 48 patients (34.8%. Rest of 90 patients remained in remission over the follow-up period of 1 year. Relapse was more common in patients below 10 years of age (47.4% as compared with older children (25.9%. Conclusion: Relapse after using methylprednisolone OMP therapy in children with vitiligo is quite common especially in younger age groups. Studies are needed to see whether these relapses could be avoided by giving the treatment for a period longer than 6 months.

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

    International Nuclear Information System (INIS)

    Novellas, Sebastien; Fournol, Maude; Geoffray, Anne; Chevallier, Patrick; Deville, Anne; Kurzenne, Jean-Yves

    2008-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-03-15

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

  6. Relapsed or refractory pediatric acute lymphoblastic leukemia: current and emerging treatments.

    Science.gov (United States)

    Martin, Alissa; Morgan, Elaine; Hijiya, Nobuko

    2012-12-01

    Relapsed acute lymphoblastic leukemia (ALL) represents a major cause of morbidity and mortality in pediatrics. With contemporary chemotherapy, >85% of patients with newly diagnosed ALL survive. Unfortunately, 20% of these patients will relapse and for these children, outcomes remain poor despite our best known chemotherapy protocols. Most of these children will achieve a second complete remission, but maintaining this remission remains difficult. Because relapsed ALL is such a significant cause of morbidity and mortality, it is the focus of much research interest. Efforts have been made and continue to focus on understanding the underlying biology that drives relapse. The role of hematopoietic stem cell transplantation in relapsed ALL remains unclear, but many clinicians still favor this for high-risk patients given the poor prognosis with current chemotherapy alone. It is important to use new drugs with little cross-resistance in the treatment of relapsed ALL. New classes of agents are currently being studied. We also discuss prognostic factors and the biology of relapsed ALL.

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

    DEFF Research Database (Denmark)

    Karlsson, Lene; Forestier, Erik; Hasle, Henrik

    2017-01-01

    Given that 30-40% of children with acute myeloid leukaemia (AML) relapse after primary therapy it is important to define prognostic factors and identify optimal therapy. From 1993 to 2012, 543 children from the Nordic countries were treated according to two consecutive protocols: 208 children...... relapsed. The influence of disease characteristics, first line treatment, relapse therapy and duration of first remission on outcome was analysed. Second complete remission (CR2) was achieved in 146 (70%) patients. Estimated 5-year overall survival (OS5y ) was 39 ± 4% for the whole group and 43 ± 4......, no allogeneic stem cell transplantation (SCT) in first remission and core binding factor AML were independent favourable prognostic factors for survival. For the 128 children (124 in CR2) that received SCT as consolidation therapy after relapse, OS5y was 61 ± 5%. Four of 19 children (21%) survived without...

  8. 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

  9. Prolonged Survival of Acute Lymphoblastic Leukemia with Intrathecal Treatments for Isolated Central Nervous System Relapse

    Directory of Open Access Journals (Sweden)

    Elan Gorshein

    2018-01-01

    Full Text Available Acute lymphoblastic leukemia is commonly cured when diagnosed in the pediatric population. It portends a poorer prognosis if present in adult patients. Although adults frequently achieve complete remission, relapse rates are substantial, particularly among the elderly and high-risk populations. In the absence of prophylactic intrathecal chemotherapy, more than half of patients may develop CNS involvement or relapse, which is associated with significant risk for systemic illness. This report describes a patient with acute lymphoblastic leukemia with repeated isolated CNS relapses. This case should remind clinicians that isolated CNS disease in the absence of systemic recurrence could successfully respond to intrathecal therapy and offer patients a favorable quality of life.

  10. Associations between neutrophil recovery time, infections and relapse in pediatric acute myeloid leukemia

    DEFF Research Database (Denmark)

    Løhmann, Ditte J A; Asdahl, Peter H; Abrahamsson, Jonas

    2018-01-01

    BACKGROUND: Children with acute myeloid leukemia (AML) treated similarly show different toxicity and leukemic responses. We investigated associations between neutrophil recovery time after the first induction course, infection and relapse in children treated according to NOPHO-AML 2004 and DB AML...

  11. Cognitive Impairment and Whole Brain Diffusion in Patients with Neuromyelitis Optica after Acute Relapse

    Science.gov (United States)

    He, Diane; Wu, Qizhu; Chen, Xiuying; Zhao, Daidi; Gong, Qiyong; Zhou, Hongyu

    2011-01-01

    The objective of this study investigated cognitive impairments and their correlations with fractional anisotropy (FA) and mean diffusivity (MD) in patients with neuromyelitis optica (NMO) without visible lesions on conventional brain MRI during acute relapse. Twenty one patients with NMO and 21 normal control subjects received several cognitive…

  12. The mortality and response rate after FLANG regimen in patients with refractory/relapsed acute leukemia

    Directory of Open Access Journals (Sweden)

    Vali A Mehrzad

    2012-01-01

    Full Text Available Background: Oncologists today are greatly concerned about the treatment of relapsed/refractory acute leukemia. FLANG regimen, combination of novantron, cytarabine, fludarabine, and granulocyte-colony stimulating factor, has been used in treatment of refractory/relapsed acute leukemia since 1990s. The present study has evaluated mortality and response rate of this regimen. Materials and Methods: In this study, 25 patients with refractory/relapsed acute leukemia aged 15-55 years underwent FLANG regimen at Seyed-Al-Shohada Hospital, Isfahan, Iran during 2008-2009. One month later, bone marrow samples were taken to evaluate the responsiveness to treatment. Participants were followed for a year. The data was analyzed by student-t and chi-square tests, logistic, and Cox regression analysis, and Kaplan-Meier curves in SPSS 19. Results: Out of the 25 patients, 8 patients (32% had acute lymphoblastic leukemia (5 refractory and 3 relapsed cases and 17 subjects had acute myeloid leukemia (7 refractory and 10 relapsed cases. According to the bone marrow biopsies taken one month after FLANG regimen, 10 patients (40% had responded to treatment. Five patients of the 10 responders underwent successful bone marrow transplantation (BMT. On the other hand, 13 patients (52%, who had not entered the CR period, died during the follow-up. Logistic regression analysis did not reveal any significant associations between disease type and responsiveness to treatment. Conclusion: This study indicated higher rates of unresponsiveness to treatment while its mortality rate was comparable with other studies. Overall, according to limitations for BMT (as the only chance for cure in Iran, it seems that FLANG therapy is an acceptable choice for these patients.

  13. [Childhood acute lymphoblastic leukemia in Norway 1992-2000].

    Science.gov (United States)

    Kolmannskog, Svein; Flaegstad, Trond; Helgestad, Jon; Hellebostad, Marit; Zeller, Bernward; Glomstein, Anders

    2007-05-31

    Acute lymphoblastic leukemia is the most common malignancy in childhood. The survival rate has increased steadily over the last 40 years. All children aged 0-15 years and diagnosed in Norway in the period 1992-2000, were included in the study (n = 301). The patients were followed up until 1.1. 2005. The diagnosis was made in 301 children, 33 new cases per year (range 24 to 40) on average. The peak incidence was between 2 and 5 years. Four of 6 infants with acute lymphoblastic leukemia and all 4 with mature B-cell leukemia are alive. Two of the remaining 291 children died before treatment was started. 289 were all treated according to the common Nordic NOPHO-ALL 1992 protocol. All children achieved remission (99.7%), except for one who died before remission was achieved. 55 children (19%) relapsed. Radiation to the brain as part of central nervous system prophylaxis was given to just 10% of the children. The 10-year event-free survival (p-EFS) was 76%, and 244 of 289 (84%) were alive 4-13 years after the diagnosis was made. The data are comparable with the best international results.

  14. 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.

  15. Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    Ramos, Nestor R.; Mo, Clifton C.; Karp, Judith E.; Hourigan, Christopher S.

    2015-01-01

    The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML) has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden to a level sufficient to meet the current criteria for “complete” remission. Nevertheless, most AML patients ultimately die from their disease, most commonly as clinically evident relapsed AML. Despite a variety of available salvage therapy options, prognosis in patients with relapsed or refractory AML is generally poor. In this review, we outline the commonly utilized salvage cytotoxic therapy interventions and then highlight novel investigational efforts currently in clinical trials using both pathway-targeted agents and immunotherapy based approaches. We conclude that there is no current standard of care for adult relapsed or refractory AML other than offering referral to an appropriate clinical trial. PMID:25932335

  16. Technical relapsed testicular irradiation for acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Velazquez Miranda, S.; Delgado Gil, M. M.; Ortiz Siedel, M.; Munoz Carmona, D. M.; Gomez-Barcelona, J.

    2011-01-01

    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.

  17. Predictors of Relapse after Discontinuing Systemic Treatment in Childhood Autoimmune Chronic Uveitis.

    Science.gov (United States)

    Simonini, Gabriele; Bracaglia, Claudia; Cattalini, Marco; Taddio, Andrea; Brambilla, Alice; De Libero, Cinzia; Pires Marafon, Denise; Caputo, Roberto; Cimaz, Rolando

    2017-06-01

    To identify clinical predictors of relapse in childhood autoimmune chronic uveitis after stopping systemic treatment. A retrospective, multicenter, cohort study. Ninety-four children in remission, receiving no treatments and with at least a 6-month followup, were enrolled. A higher probability of maintaining remission after discontinuing treatment was shown in idiopathic compared with juvenile idiopathic arthritis uveitis (Mantel-Cox chi-square = 23.21) if inactivity had been obtained within 6 months from starting systemic treatment (Mantel-Cox chi-square = 24.17) and by antitumor necrosis factor-α treatment (Mantel-Cox chi-square = 6.43). Type of disease, time, and type of systemic therapy to achieve inactivity predict different duration of uveitis remission after treatment withdrawal.

  18. 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.

  19. Acute Non-Traumatic Abdominal Pain in Childhood at Kenyatta ...

    African Journals Online (AJOL)

    Background The assessment and diagnosis of acute abdominal pain in childhood is clinically challenging. The epidemiologic correlates differ for different paediatric age groups and settings. Objectives To determine the clinical spectrum of acute abdominal pain in childhood at a referral Kenyan public hospital. Design

  20. Epigenetic analysis of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Dunwell, Thomas L; Hesson, Luke B; Pavlova, Tatiana; Zabarovska, Veronika; Kashuba, Vladimir; Catchpoole, Daniel; Chiaramonte, Raffaella; Brini, Anna T; Griffiths, Mike; Maher, Eamonn R; Zabarovsky, Eugene; Latif, Farida

    2009-04-01

    We used a chromosome 3 wide NotI microarray for identification of epigenetically inactivated genes in childhood acute lymphoblastic leukemia (ALL). Three novel genes demonstrated frequent methylation in childhood ALL. PPP2R3A (protein phosphatase 2, regulatory subunit B", alpha) was frequently methylated in T (69%) and B (82%)-ALL. Whilst FBLN2 (fibulin 2) and THRB (thyroid hormone receptor, beta) showed frequent methylation in B-ALL (58%; 56% respectively), but were less frequently methylated in T-ALL (17% for both genes). Recently it was demonstrated that BNC1 (Basonuclin 1) and MSX1 (msh homeobox 1) were frequently methylated across common epithelial cancers. In our series of childhood ALL BNC1 was frequently methylated in both T (77%) and B-ALL (79%), whilst MSX1 showed T-ALL (25%) specific methylation. The methylation of the above five genes was cancer specific and expression of the genes could be restored in methylated leukemia cell lines treated with 5-aza-2'-deoxycytidine. This is the first report demonstrating frequent epigenetic inactivation of PPP2R3A, FBLN2, THRB, BNC1 and MSX1 in leukemia. The identification of frequently methylated genes showing cancer specific methylation will be useful in developing early cancer detection screens and for targeted epigenetic therapies.

  1. Relapsing acute myeloid leukemia presenting as hypopyon uveitis

    Directory of Open Access Journals (Sweden)

    Sapna P Hegde

    2011-01-01

    Full Text Available Anterior segment infiltration in acute myeloid leukemia (AML presenting as hypopyon uveitis is very rare. We report this case as an uncommon presentation in a patient on remission after bone marrow transplant for AML. In addition to the hypopyon, the patient presented with "red eye" caused by ocular surface disease due to concurrent graft-versus-host disease and glaucoma. The classical manifestations of masquerade syndrome due to AML were altered by concurrent pathologies. Media opacities further confounded the differential diagnosis. We highlight the investigations used to arrive at a definitive diagnosis. In uveitis, there is a need to maintain a high index of clinical suspicion, as early diagnosis in ocular malignancy can save sight and life.

  2. Relapsing acute disseminated encephalomyelitis associated with chronic Epstein-Barr virus infection: MRI findings

    International Nuclear Information System (INIS)

    Shoji, H.; Kusuhara, T.; Honda, Y.; Hino, H.; Kojima, K.; Abe, T.; Watanabe, M.

    1992-01-01

    A 25-year-old women had a fever, left cervical lymphadenopathy, neurological symptoms and signs, CSF pleocytosis and persistent high serum antibodies to the Epstein-Barr virus (EBV); she had a recurrence 1 year later. She was thought to have relapsing acute disseminated encephalomyelitis associated with chronic EBV infection. MRI revealed abnormalities, mainly in the right basal ganglia and left midbrain. At the time of the recurrence, further abnormalities appeared in the opposite basal ganglia and right cerebral white matter. (orig.)

  3. Relapsing acute disseminated encephalomyelitis associated with chronic Epstein-Barr virus infection: MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Shoji, H.; Kusuhara, T.; Honda, Y.; Hino, H. (1. Dept. (Neurology) of Internal Medicine, Kurume Univ. School of Medicine (Japan)); Kojima, K.; Abe, T. (Dept. of Radiology, Kurume Univ. School of Medicine (Japan)); Watanabe, M. (Dept. of Neurosurgery, Koyanagi Hospital, Saga (Japan))

    1992-08-01

    A 25-year-old women had a fever, left cervical lymphadenopathy, neurological symptoms and signs, CSF pleocytosis and persistent high serum antibodies to the Epstein-Barr virus (EBV); she had a recurrence 1 year later. She was thought to have relapsing acute disseminated encephalomyelitis associated with chronic EBV infection. MRI revealed abnormalities, mainly in the right basal ganglia and left midbrain. At the time of the recurrence, further abnormalities appeared in the opposite basal ganglia and right cerebral white matter. (orig.).

  4. The prognostic significance of early treatment response in pediatric relapsed acute myeloid leukemia : results of the international study Relapsed AML 2001/01

    NARCIS (Netherlands)

    Creutzig, Ursula; Zimmermann, Martin; Dworzak, Michael N.; Gibson, Brenda; Tamminga, Rienk; Abrahamsson, Jonas; Ha, Shau-Yin; Hasle, Henrik; Maschan, Alexey; Bertrand, Yves; Leverger, Guy; von Neuhoff, Christine; Razzouk, Bassem; Rizzari, Carmelo; Smisek, Petr; Smith, Owen P.; Stark, Batia; Reinhardt, Dirk; Kaspers, Gertjan L.

    2014-01-01

    The prognostic significance of early response to treatment has not been reported in relapsed pediatric acute myeloid leukemia. In order to identify an early and easily applicable prognostic factor allowing subsequent treatment modifications, we assessed leukemic blast counts in the bone marrow by

  5. Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia

    DEFF Research Database (Denmark)

    Craddock, Charles; Labopin, Myriam; Robin, Marie

    2016-01-01

    Disease relapse is the most common cause of treatment failure after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes, yet treatment options for such patients remain extremely limited. Azacitidine is an important new therapy in high-risk myelodysplastic...... syndromes and acute myeloid leukemia but its role in patients who relapse post allograft has not been defined. We studied the tolerability and activity of azacitidine in 181 patients who relapsed after an allograft for acute myeloid leukemia (n=116) or myelodysplastic syndromes (n=65). Sixty-nine patients...... conclude that azacitidine represents an important new therapy in selected patients with acute myeloid leukemia/myelodysplastic syndromes who relapse after allogeneic stem cell transplantation. Prospective studies to confirm optimal treatment options in this challenging patient population are required....

  6. Dynamics of myeloid cell populations during relapse-preventive immunotherapy in acute myeloid leukemia.

    Science.gov (United States)

    Rydström, Anna; Hallner, Alexander; Aurelius, Johan; Sander, Frida Ewald; Bernson, Elin; Kiffin, Roberta; Thoren, Fredrik Bergh; Hellstrand, Kristoffer; Martner, Anna

    2017-08-01

    Relapse of leukemia in the postchemotherapy phase contributes to the poor prognosis and survival in patients with acute myeloid leukemia (AML). In an international phase IV trial (ClinicalTrials.gov; NCT01347996), 84 patients with AML in first complete remission who had not undergone transplantation received immunotherapy with histamine dihydrochloride (HDC) and low-dose IL-2 with the aim of preventing relapse. The dynamics of myeloid cell counts and expression of activation markers was assessed before and after cycles of immunotherapy and correlated with clinical outcome in terms of relapse risk and survival. During cycles, a pronounced increase in blood eosinophil counts was observed along with a reduction in monocyte and neutrophil counts. A strong reduction of blood monocyte counts during the first HDC/IL-2 treatment cycle predicted leukemia-free survival. The HDC component of the immunotherapy exerts agonist activity at histamine type 2 receptors (H2Rs) that are expressed by myeloid cells. It was observed that the density of H 2 R expression in blood monocytes increased during cycles of immunotherapy and that high monocyte H 2 R expression implied reduced relapse risk and improved overall survival. Several other activation markers, including HLA-DR, CD86, and CD40, were induced in monocytes and dendritic cells during immunotherapy but did not predict clinical outcome. In addition, expression of HLA-ABC increased in all myeloid populations during therapy. A low expression of HLA-ABC was associated with reduced relapse risk. These results suggest that aspects of myeloid cell biology may impact clinical benefit of relapse-preventive immunotherapy in AML. © Society for Leukocyte Biology.

  7. 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

  8. 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......, Denmark, Germany, Japan, UK and US to determine death or relapse up to 10 years from diagnosis. Adjusting for known prognostic factors, we calculated hazard ratios (HRs) and 95% confidence intervals (CI) for overall survival and event-free survival for ELF-MF exposure categories and by 0.1 μT increases...

  9. 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.

  10. Hematopoietic stem cell transplantation for isolated extramedullary relapse of acute lymphoblastic leukemia in children.

    Science.gov (United States)

    Gabelli, Maria; Zecca, Marco; Messina, Chiara; Carraro, Elisa; Buldini, Barbara; Rovelli, Attilio Maria; Fagioli, Franca; Bertaina, Alice; Lanino, Edoardo; Favre, Claudio; Rabusin, Marco; Prete, Arcangelo; Ripaldi, Mimmo; Barberi, Walter; Porta, Fulvio; Caniglia, Maurizio; Santarone, Stella; D'Angelo, Paolo; Basso, Giuseppe; Locatelli, Franco

    2018-06-13

    Relapse of acute lymphoblastic leukemia (ALL) may occur in extramedullary sites, mainly central nervous system (CNS) and testis. Optimal post-remissional treatment for isolated extramedullary relapse (IEMR) is still controversial. We collected data of children treated with hematopoietic stem cell transplantation (HSCT) for ALL IEMR from 1990 to 2015 in Italy. Among 281 patients, 167 had a relapse confined to CNS, 73 to testis, 14 to mediastinum, and 27 to other organs. Ninety-seven patients underwent autologous HSCT, 79 received allogeneic HSCT from a matched family donor, 75 from a matched unrelated donor, and 30 from an HLA-haploidentical donor. The 10-year overall survival was 56% and was not influenced by gender, ALL blast immune-phenotype, age, site of relapse, duration of first remission, and type of HSCT. In multivariable analysis, the only prognostic factors were disease status at HSCT and year of transplantation. Patients transplanted in third or subsequent complete remission (CR) had a risk of death 2.3 times greater than those in CR2. Children treated after 2000 had half the risk of death than those treated before that year. Our results suggest that both autologous and allogeneic HSCT may be considered for the treatment of pediatric ALL IEMR after the achievement of CR2.

  11. Renal, gastrointestinal, and hepatic late effects in survivors of childhood acute myeloid leukemia treated with chemotherapy only--a NOPHO-AML study

    DEFF Research Database (Denmark)

    Skou, Anne-Sofie; Glosli, Heidi; Jahnukainen, Kirsi

    2014-01-01

    BACKGROUND: We investigated the spectrum, frequency, and risk factors for renal, gastrointestinal, and hepatic late adverse effects in survivors of childhood acute myeloid leukemia (AML) without relapse treated with chemotherapy alone according to three consecutive AML trials by the Nordic Society...

  12. [Acute scrotal pain in childhood: legal pitfalls].

    Science.gov (United States)

    Bader, Pia; Hugemann, Christoph; Frohneberg, Detlef

    2017-12-01

    Acute scrotal pain in childhood is an emergency.Sudden scrotal pain may be caused by a variety of diseases. Therefore, it is important to carefully consider the specific medical history and possible differential diagnoses in each case for fast and decisive action (e. g. in case of testicular torsion). As minors lack the capacity for consent, it is absolutely necessary to obtain consent from their legal guardian. However, obtaining consent in the available time frame can cause organisational challenges in an acute emergency, which may lead to situations in the daily routine where a therapeutic decision needs to be taken (including surgery) without legal security based on consent by the guardian. In some cases, the child's consent also needs to be taken into account, depending on its age and development.For the physician and surgeon in charge, the legal evaluation of the case at hand and therewith the obtainment of legal security are of great significance. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Childhood Acute Myeloid Leukemia Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Childhood acute myeloid leukemia and other myeloid malignancies treatment may include chemotherapy, radiation therapy, stem cell transplant, and targeted therapy. Learn more about AML and myelodysplastic/myeloproliferative diseases in this expert-reviewed summary.

  14. Leydig cell function in boys following treatment for testicular relapse of acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Blatt, J.; Sherins, R.J.; Niebrugge, D.; Bleyer, W.A.; Poplack, D.G.

    1985-01-01

    Current practice for achieving local control of testicular relapse in males with acute lymphoblastic leukemia (ALL) includes the use of 2,400-rad testicular radiation. Although this therapy is known to cause germ cell depletion, it has been assumed that it does not alter testicular secretion of testosterone. To test this assumption, the authors measured gonadotropin and testosterone levels in seven boys with ALL who had been treated with radiation for clinically apparent testicular relapse. In four of seven boys, testicular relapse was bilateral with overt involvement of one testicle and microscopic involvement of the other. Three of these four boys demonstrated delayed sexual maturation, and in addition to elevated follicle-stimulating hormone (FSH) concentrations, testosterone levels were low and luteinizing hormone levels were elevated compared with controls. These data indicate that boys with overt testicular leukemia who are treated with 2,400-rad testicular radiation are at risk for Leydig cell dysfunction. However, the relative contributions of radiation, prior chemotherapy, and leukemic infiltration to this dysfunction remain to be clarified

  15. 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

  16. Jab1/Csn5-Thioredoxin Signaling in Relapsed Acute Monocytic Leukemia under Oxidative Stress.

    Science.gov (United States)

    Zhou, Fuling; Pan, Yunbao; Wei, Yongchang; Zhang, Ronghua; Bai, Gaigai; Shen, Qiuju; Meng, Shan; Le, Xiao-Feng; Andreeff, Michael; Claret, Francois X

    2017-08-01

    Purpose: High levels of ROS and ineffective antioxidant systems contribute to oxidative stress, which affects the function of hematopoietic cells in acute myeloid leukemia (AML); however, the mechanisms by which ROS lead to malignant transformation in relapsed AML-M5 are not completely understood. We hypothesized that alterations in intracellular ROS would trigger AML-M5 relapse by activating the intrinsic pathway. Experimental Design: We studied ROS levels and conducted c-Jun activation domain-binding protein-1 ( JAB1/COPS5 ) and thioredoxin ( TRX ) gene expression analyses with blood samples obtained from 60 matched AML-M5 patients at diagnosis and relapse and conducted mechanism studies of Jab1's regulation of Trx in leukemia cell lines. Results: Our data showed that increased production of ROS and a low capacity of antioxidant enzymes were characteristics of AML-M5, both at diagnosis and at relapse. Consistently, increased gene expression levels of TRX and JAB1/COPS5 were associated with low overall survival rates in patients with AML-M5. In addition, stimulating AML-M5 cells with low concentrations of hydrogen peroxide led to increased Jab1 and Trx expression. Consistently, transfection of ectopic Jab1 into leukemia cells increased Trx expression, whereas silencing of Jab1 in leukemia cells reduced Trx expression. Mechanistically, Jab1 interacted with Trx and stabilized Trx protein. Moreover, Jab1 transcriptionally regulated Trx. Furthermore, depletion of Jab1 inhibited leukemia cell growth both in vitro and in vivo Conclusions: We identified a novel Jab1-Trx axis that is a key cellular process in the pathobiologic characteristics of AML-M5. Targeting the ROS/Jab1/Trx pathway could be beneficial in the treatment of AML-M5. Clin Cancer Res; 23(15); 4450-61. ©2017 AACR . ©2017 American Association for Cancer Research.

  17. Benign acute childhood myositis: an unusual cause of calf pain

    Energy Technology Data Exchange (ETDEWEB)

    Panghaal, Vikash; Levin, Terry L. [Montefiore Medical Center, Department of Radiology, Bronx, NY (United States); Ortiz-Romero, Sara [Albert Einstein College of Medicine, Bronx, NY (United States); Lovinsky, Stephanie [Montefiore Medical Center, Department of Pediatrics, Bronx, NY (United States)

    2008-06-15

    We present a 17-year-old boy with benign acute childhood myositis (BACM) who presented with acute onset of right calf pain, swelling, and difficulty walking. The MR findings are reviewed. MR may be useful in diagnosing BACM and in differentiating it from other causes of myositis. (orig.)

  18. Benign acute childhood myositis: an unusual cause of calf pain

    International Nuclear Information System (INIS)

    Panghaal, Vikash; Levin, Terry L.; Ortiz-Romero, Sara; Lovinsky, Stephanie

    2008-01-01

    We present a 17-year-old boy with benign acute childhood myositis (BACM) who presented with acute onset of right calf pain, swelling, and difficulty walking. The MR findings are reviewed. MR may be useful in diagnosing BACM and in differentiating it from other causes of myositis. (orig.)

  19. Relapsed acute promyelocytic leukemia in a hemodialysis-dependent patient treated with arsenic trioxide: a case report

    Directory of Open Access Journals (Sweden)

    Emmons Gregory S

    2012-10-01

    Full Text Available Abstract Introduction In the relapsed setting, arsenic trioxide remains the backbone of treatment. Scant literature exists regarding treatment of relapsed acute promyelocytic leukemia in patients with renal failure. To the best of our knowledge we are the first to report a safe and effective means of treatment for relapsed acute promyelocytic leukemia in the setting of advanced renal failure, employing titration of arsenic trioxide based on clinical parameters rather than arsenic trioxide levels. Case presentation A 33-year-old Caucasian man with a history of acute promyelocytic leukemia in remission for 3 years, as well as dialysis-dependent chronic renal failure secondary to a solitary kidney and focal segmental glomerulosclerosis and human immunodeficiency virus infection, receiving highly active antiretroviral therapy presented to our hospital with bone marrow biopsy-confirmed relapsed acute promyelocytic leukemia. Arsenic trioxide was begun at a low dose with dose escalation based only on side effect profile monitoring and not laboratory testing for induction as well as maintenance without undue toxicity. Our patient achieved and remains in complete hematologic and molecular remission as of this writing. Conclusion Arsenic trioxide can be used safely and effectively to treat acute promyelocytic leukemia in patients with advanced renal failure using careful monitoring of side effects rather than blood levels of arsenic to guide therapeutic dosing.

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

    Science.gov (United States)

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

    2017-11-01

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

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

    Science.gov (United States)

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

    2011-06-01

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

  2. Risk of venous thromboembolism in neuromyelitis optica patients hospitalized for acute relapse.

    Science.gov (United States)

    Farber, Rebecca Straus; Gross, Robert; Zakin, Elina; Fabian, Michelle

    2017-06-01

    Neuromyelitis optica spectrum disorder (NMOSD) patients may be at increased risk of venous thromboembolism (VTE) not only due to ambulatory disability but also due to systemic autoimmune and inflammatory mechanisms altering the hemostatic balance. To compare the risk of VTE in NMOSD versus multiple sclerosis (MS) patients hospitalized for acute relapses. Hospital admissions for MS or NMOSD exacerbations were retrospectively identified. Demographics and medical history were recorded. The relationship between visit diagnosis and presence of VTE within 6 weeks of relapse onset was assessed by univariate logistic regression. A multivariate model evaluated the relationship between diagnosis, age, race, gender, body mass index (BMI), disease modifying therapy use, oral corticosteroid use, oral contraceptive use, smoking, length of stay (LOS), and ambulatory status on VTE risk. A total of 30 NMOSD patients had 55 hospitalizations; 179 MS patients had 264 hospitalizations. Six NMOSD patients and one MS patient had VTE. NMOSD visits compared to MS visits had an odds ratio (OR) of VTE of 32.2 ( p = 0.002). NMOSD was more likely to be associated with VTE (OR = 17.4; p = 0.01) controlling for age, LOS, and ambulatory disability. NMOSD may be a risk factor for VTE. Larger prospective studies are required to confirm this risk and determine implications for prophylaxis.

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

    DEFF Research Database (Denmark)

    Søegaard, Signe Holst; Rostgaard, Klaus; Schmiegelow, Kjeld

    2017-01-01

    information on ALL subtypes. Using Cox regression, we estimated hazard ratios (HRs) comparing vaccinated with unvaccinated children.Results: Childhood ALL was diagnosed in 490 children during 10 829 194 person-years of follow-up. Neither the total number of vaccine doses received nor exposure to each......Background: It has been proposed that childhood vaccinations protect against acute lymphoblastic leukaemia (ALL) in children by modulation of future responses to common infections in childhood. However, the available studies provide inconsistent findings, and population-based cohort studies...... with longitudinal information on vaccinations are lacking.Methods: In a register-based cohort of all children born in Denmark from 1 January 1990 to 31 December 2008, followed up until age 15 years or 31 December 2009 (n=1 225 404), we evaluated exposure to childhood vaccination and risk of childhood ALL, including...

  4. Recovery from an acute relapse is associated with changes in motor resting-state connectivity in multiple sclerosis

    DEFF Research Database (Denmark)

    Dogonowski, Anne-Marie; Blinkenberg, Morten; Paulson, Olaf B.

    2016-01-01

    Resting-state functional MRI (rs-fMRI) of the brain has been successfully used to identify altered functional connectivity in the motor network in multiple sclerosis (MS).1 In clinically stable patients with MS, we recently demonstrated increased coupling between the basal ganglia and the motor...... network.1 Accordingly, rs-fMRI in MS is particularly suited to investigate functional reorganisation of the motor network in the remission phase after a relapse because the resting-state connectivity pattern is not influenced by interindividual differences in motor ability and task performance....... In this prospective rs-fMRI study, we mapped acute changes in resting-state motor connectivity in 12 patients with relapsing forms of MS presenting with an acute relapse involving an upper limb paresis. Previous functional MRI (fMRI) studies have shown that the activation of sensorimotor areas was stronger and more...

  5. Extending supplementary feeding for children younger than 5 years with moderate acute malnutrition leads to lower relapse rates

    Science.gov (United States)

    Children with moderate acute malnutrition (MAM) have a high rate of relapse and death in the year following recovery. In this pilot study, we evaluate the long-term benefits of an extended course of nutritional therapy for children with MAM. Rural Malawian children 6 to 59 months old with MAM, defin...

  6. Relapses from acute malnutrition and related factors in a community-based management programme in Burkina Faso.

    Science.gov (United States)

    Somassè, Yassinmè Elysée; Dramaix, Michèle; Bahwere, Paluku; Donnen, Philippe

    2016-10-01

    Community-based management of acute malnutrition (CMAM) is effective in treating acute malnutrition. However, post-discharge follow-up often lacks. We aimed at assessing the relapse rate and the associated factors in a CMAM programme in Burkina Faso. Discharged children from the community nutrition centre were requested to return at least every 3 months for follow-up. The data of recovered children (weight-for-height z-score ≥-2) who were discharged between July 2010 and June 2011 were collected in 45 villages, randomly selected out of 210 in January 2012. Sociodemographic data, economic variables, information on household food availability and the child's food consumption in the last 24 h were collected from the parents. A multivariate Cox proportional hazards regression was used to identify the factors associated to relapse. Of the 637 children, 14 (2.2%) died and 218 (34.2%) were lost to follow-up. The relapse rate [95% confidence interval] among the children who returned for follow-up was 15.4 [11.8-19.0] per 100 children-years. The associated factors to relapses in multivariate Cox regression model were mid-upper arm circumference (MUAC) at discharge below 125 mm, no oil/fat consumption during the last 24 h and incomplete vaccination. To limit relapses, CMAM programmes should avoid premature discharge before a MUAC of at least 125 mm. Nutrition education should emphasize fat/oil as inexpensive energy source for children. Promoting immunization is essential to promote child growth. Periodic monitoring of discharged children should be organized to detect earlier those who are at risk of relapse. The relapse rate should be a CMAM effectiveness indicator. © 2015 John Wiley & Sons Ltd.

  7. 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...

  8. 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...

  9. Increase in hospital admissions for acute childhood asthma in Cape ...

    African Journals Online (AJOL)

    To determine whether hospital admissions for acute childhood asthma were rising in Cape Town in line with the experience of other countries, Red Cross War Memorial Children's Hospital's records for the period 1978 - 1990 were analysed. These were compared with total admissions for non-surgical causes and lower ...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  11. Management of acute moderate and severe childhood malnutrition

    Science.gov (United States)

    Acute childhood malnutrition affects about a tenth of the world's children under 5 years of age, particularly those living in circumstances of extreme poverty in the developing world. Malnutrition is typically the result of an inadequate diet and is one of the most common diagnoses in children in he...

  12. Maintenance therapy of childhood acute lymphoblastic leukemia revisited—Should drug doses be adjusted by white blood cell, neutrophil, or lymphocyte counts?

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: 6-Mercaptopurine (6MP) and methotrexate (MTX) based maintenance therapy is a critical phase of childhood acute lymphoblastic leukemia treatment. Wide interindividual variations in drug disposition warrant frequent doses adjustments, but there is a lack of international consensus on dose...... levels of 6-thioguanine nucleotides or MTX (including its polyglutamates) to be significant relapse predictors. The parameters significantly associated with risk of relapse (N = 83) were male sex (hazard ratio [HR] 2.0 [1.3-3.1], P = 0.003), WBC at diagnosis (HR = 1.04 per 10 × 10(9) /l rise [1...

  13. Osteogenic toxicity in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet)

    2013-01-01

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

  14. The importance of monitoring minimal residual disease in childhood acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Kolenova, A.; Subova, Z.; Cizmar, A.; Sejnova, D.; Kaiserova, E.; Hikkel, I.; Hikkelova, M.; Bubanska, E.; Oravkinova, I.

    2012-01-01

    Since the strong correlation between minimal residual disease (MRD) levels and risk of relapse in childhood acute lymphoblastic leukemia, monitoring of MRD provides unique information regarding treatment response. Because the significance of MRD monitoring has been strongly supported by several studies and because it has been implemented in the latest protocols, there has been a significant effort to develop MRD monitoring in the Slovak Republic. Between 1. 10. 2006 and 31. 12. 2009, 50 children with ALL who were treated at three Slovak centers were included in the RQ PCR MRD pilot project. Based on MRD stratification, we identified 26 patients who were stratified into the HRG (high risk group) 3 patients (11,5 %), IRG (intermediate risk group), 14 p. 54 % and SRG (standard risk group), 9 p. (34,5 %). (author)

  15. Acute Renal Failure In Infancy and Childhood

    African Journals Online (AJOL)

    1974-10-19

    Oct 19, 1974 ... Single kidney + calculus in ureter ... Calculus in one ureter + acute glomeru- lonephritis ... Ureteric ... A careful history and physical examination will often provide clues to ..... variation in response and tolerance occurs; frequent.

  16. 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.

  17. Relapsing polychondritis in childhood: a rare observation studied by CT and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Oddone, M. (Dept. of Radiology, G. Gaslini Children' s Research Inst., Genoa (Italy)); Toma, P. (Dept. of Radiology, G. Gaslini Children' s Research Inst., Genoa (Italy)); Taccone, A. (Dept. of Radiology, G. Gaslini Children' s Research Inst., Genoa (Italy)); Hanau, G. (Dept. of Auxology, Genoa Univ. (Italy)); Delogu, A. (Dept. of Auxology, Genoa Univ. (Italy)); Gemme, G. (Dept. of Auxology, Genoa Univ. (Italy))

    1992-11-01

    Relapsing polychondritis is very rare in children. The diagnosis must be based on a combination of clinical and pathologic features. CT is very useful for an accurate and rapid assessment of laryngo-tracheo-bronchial involvement and the typical finding is lumen narrowing by wall thickening and collapse of the supporting cartilaginous structures. The role of MR imaging should be complementary to CT. (orig.)

  18. Anti-Erwinia asparaginase antibodies during treatment of childhood acute lymphoblastic leukemia and their relationship to outcome

    DEFF Research Database (Denmark)

    Albertsen, BK; Schmiegelow, Kjeld; Schrøder, Henrik

    2002-01-01

    PURPOSE: A case-control study was performed to determine whether patients who had been treated with Erwinia asparaginase as part of their treatment for childhood acute lymphoblastic leukemia (ALL) and who showed relapsed of their disease more often developed anti-asparaginase antibodies than...... (median follow-up 70 months). Anti- Erwinia asparaginase antibodies were measured (ELISA method) during maintenance therapy after asparaginase treatment (30,000 IU/m(2) daily for 10 days in all patients plus twice weekly for 2 weeks in intermediate-risk and high-risk ALL patients). RESULTS: The overall...... incidence of anti- Erwinia asparaginase antibodies was 8% (3 of 39 patients). There was no statistically significant difference in the incidence of antibody formation between patients who had suffered relapse (1 of 13) and those who had not (2 of 26). In two of the three patients who developed antibodies...

  19. Prognosis and treatment after relapse of acute lymphoblastic leukemia and non-Hodgkin's lymphoma: 1985. A report from the Childrens Cancer Study Group

    International Nuclear Information System (INIS)

    Bleyer, W.A.; Sather, H.; Hammond, G.D.

    1986-01-01

    Acute lymphoblastic leukemia and non-Hodgkin's lymphoma constitute 42% to 45% of the cancers in infants, children, and adolescents: In 1985, an estimated 2025 children were newly diagnosed with these two cancers and 900 (43%) of the pediatric cancer deaths in the United States have been projected to be due to these diseases. The single most important obstacle to preventing these deaths is relapse, and prevention of relapse or salvage of the patient who has had a relapse continues to be a major therapeutic challenge. The most important initial step in the treatment of the child whose disease has relapsed is to determine, to the extent possible, the prognosis. In a child with non-Hodgkin's lymphoma, a relapse confers an extremely poor prognosis, regardless of site of relapse, tumor histology, or other original prognostic factors, prior therapy, or time to relapse. In the child with acute lymphoblastic leukemia in relapse, the prognosis depends on multiple factors. The primary therapy is chemotherapy or chemoradiotherapy with marrow grafting. Other options exist, including no therapy, or investigational therapy. The therapy selected should be predicated on the prognosis. In the child with an isolated central nervous system (CNS) relapse off therapy, minimum therapy should be administered, particularly if the relapse occurred without prior cranial irradiation. In the child whose relapse is more than 6 months off therapy, conventional therapy should be considered. Also, a patient with an isolated CNS relapse on therapy after prior cranial irradiation should be given moderate therapy. Bone marrow transplantation or high-dose chemoradiotherapy with autologous marrow rescue should be reserved in children with a second or subsequent extramedullary relapse, and possibly for those with a first isolated overt testicular relapse on therapy

  20. Factors Associated with Long-Term Risk of Relapse after Unrelated Cord Blood Transplantation in Children with Acute Lymphoblastic Leukemia in Remission.

    Science.gov (United States)

    Page, Kristin M; Labopin, Myriam; Ruggeri, Annalisa; Michel, Gerard; Diaz de Heredia, Cristina; O'Brien, Tracey; Picardi, Alessandra; Ayas, Mouhab; Bittencourt, Henrique; Vora, Ajay J; Troy, Jesse; Bonfim, Carmen; Volt, Fernanda; Gluckman, Eliane; Bader, Peter; Kurtzberg, Joanne; Rocha, Vanderson

    2017-08-01

    For pediatric patients with acute lymphoblastic leukemia (ALL), relapse is an important cause of treatment failure after unrelated cord blood transplant (UCBT). Compared with other donor sources, relapse is similar or even reduced after UCBT despite less graft-versus-host disease (GVHD). We performed a retrospective analysis to identify risk factors associated with the 5-year cumulative incidence of relapse after UCBT. In this retrospective, registry-based study, we examined the outcomes of 640 children (leukemia-free survival (LFS), and relapse were 59%, 52%, and 23%, respectively. In multivariate analysis (MVA), acute GVHD (grades II to IV) and TBI protected against relapse. In patients in CR2, rates of 5-year OS, LFS, and the cumulative incidence of relapse were 46%, 44%, and 28%, respectively. In MVA, longer duration from diagnosis to UCBT (≥30 months) and TBI were associated with decreased relapse risk. Importantly, receiving a fully HLA matched graft was a strong risk factor for increased relapse in MVA. An exploratory analysis of all 640 patients supported the important association between the presence of acute GVHD and less relapse but also demonstrated an increased risk of nonrelapse mortality. In conclusion, the impact of GVHD as a graft-versus-leukemia marker is evident in pediatric ALL after UCBT. Strategies that promote graft-versus-leukemia while harnessing GVHD should be further investigated. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  1. Acute acquired comitant esotropia of childhood

    DEFF Research Database (Denmark)

    Hesgaard, Helena; Vinding, Troels

    2015-01-01

    acute onset of comitant esotropia, available data on ophthalmologic, orthoptic and neurologic examinations. Children with neurological signs, AACE recurrence or hyperopia followed. RESULTS...... no obvious neurological signs at onset. Four significant risk factors for intracranial disease were identified as follows: larger esodeviation at distance, recurrence of AACE, neuro signs (papilledema) and older age at onset (>6 years). CONCLUSION: In a large case series of children with AACE and by review...

  2. Beyond CD19: Opportunities for future development of targeted immunotherapy in pediatric relapsed-refractory acute leukemia

    Directory of Open Access Journals (Sweden)

    Haneen eShalabi

    2015-10-01

    Full Text Available Chimeric antigen receptor (CAR T cell therapy has been used as a targeted approach in cancer therapy. Relapsed and refractory acute leukemia in pediatrics has been difficult to treat with conventional therapy due to dose limiting toxicities. With the recent success of CD 19 CAR in pediatric patients with B cell ALL, this mode of therapy has become a very attractive option for these patients with high risk disease. In this review, we will discuss current treatment paradigms of pediatric acute leukemia, and potential therapeutic targets for additional high risk populations, including T cell ALL, AML, and infant ALL.

  3. Treatment of acute relapses in multiple sclerosis at home with oral dexamethasone : a pilot study

    NARCIS (Netherlands)

    De Keyser, J; Zwanikken, C; Zorgdrager, A; Oenema, D

    The objective of this study was to investigate the feasibility of treating relapses of multiple sclerosis (MS) at home with oral dexamethasone. Twenty-five out of 28 consecutive patients with MS who presented with a relapse of less than 2 weeks' duration were treated on an open basis with oral

  4. Clinical significance of productive immunoglobulin heavy chain gene rearrangements in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Katsibardi, Katerina; Braoudaki, Maria; Papathanasiou, Chrissa; Karamolegou, Kalliopi; Tzortzatou-Stathopoulou, Fotini

    2011-09-01

    We analyzed the CDR3 region of 80 children with B-cell acute lymphoblastic leukemia (B-ALL) using the ImMunoGeneTics Information System and JOINSOLVER. In total, 108 IGH@ rearrangements were analyzed. Most of them (75.3%) were non-productive. IGHV@ segments proximal to IGHD-IGHJ@ were preferentially rearranged (45.3%). Increased utilization of IGHV3 segments IGHV3-13 (11.3%) and IGHV3-15 (9.3%), IGHD3 (30.5%), and IGHJ4 (34%) was noted. In pro-B ALL more frequent were IGHV3-11 (33.3%) and IGHV6-1 (33.3%), IGHD2-21 (50%), IGHJ4 (50%), and IGHJ6 (50%) segments. Shorter CDR3 length was observed in IGHV@6, IGHD7, and IGHJ1 segments, whereas increased CDR3 length was related to IGHV3, IGHD2, and IGHJ4 segments. Increased risk of relapse was found in patients with productive sequences. Specifically, the relapse-free survival rate at 5 years in patients with productive sequences at diagnosis was 75% (standard error [SE] ±9%), whereas in patients with non-productive sequences it was 97% (SE ±1.92%) (p-value =0.0264). Monoclonality and oligoclonality were identified in 81.2% and 18.75% cases at diagnosis, respectively. Sequence analysis revealed IGHV@ to IGHDJ joining only in 6.6% cases with oligoclonality. The majority (75%) of relapsed patients had monoclonal IGH@ rearrangements. The preferential utilization of IGHV@ segments proximal to IGHDJ depended on their location on the IGHV@ locus. Molecular mechanisms occurring during IGH@ rearrangement might play an essential role in childhood ALL prognosis. In our study, the productivity of the rearranged sequences at diagnosis proved to be a significant prognostic factor.

  5. HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse.

    Science.gov (United States)

    Martelli, Massimo F; Di Ianni, Mauro; Ruggeri, Loredana; Falzetti, Franca; Carotti, Alessandra; Terenzi, Adelmo; Pierini, Antonio; Massei, Maria Speranza; Amico, Lucia; Urbani, Elena; Del Papa, Beatrice; Zei, Tiziana; Iacucci Ostini, Roberta; Cecchini, Debora; Tognellini, Rita; Reisner, Yair; Aversa, Franco; Falini, Brunangelo; Velardi, Andrea

    2014-07-24

    Posttransplant relapse is still the major cause of treatment failure in high-risk acute leukemia. Attempts to manipulate alloreactive T cells to spare normal cells while killing leukemic cells have been unsuccessful. In HLA-haploidentical transplantation, we reported that donor-derived T regulatory cells (Tregs), coinfused with conventional T cells (Tcons), protected recipients against graft-versus-host disease (GVHD). The present phase 2 study investigated whether Treg-Tcon adoptive immunotherapy prevents posttransplant leukemia relapse. Forty-three adults with high-risk acute leukemia (acute myeloid leukemia 33; acute lymphoblastic leukemia 10) were conditioned with a total body irradiation-based regimen. Grafts included CD34(+) cells (mean 9.7 × 10(6)/kg), Tregs (mean 2.5 × 10(6)/kg), and Tcons (mean 1.1 × 10(6)/kg). No posttransplant immunosuppression was given. Ninety-five percent of patients achieved full-donor type engraftment and 15% developed ≥grade 2 acute GVHD. The probability of disease-free survival was 0.56 at a median follow-up of 46 months. The very low cumulative incidence of relapse (0.05) was significantly better than in historical controls. These results demonstrate the immunosuppressive potential of Tregs can be used to suppress GVHD without loss of the benefits of graft-versus-leukemia (GVL) activity. Humanized murine models provided insights into the mechanisms underlying separation of GVL from GVHD, suggesting the GVL effect is due to largely unopposed Tcon alloantigen recognition in bone marrow. © 2014 by The American Society of Hematology.

  6. Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

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

    2017-01-01

    BACKGROUND: Survival for childhood acute lymphoblastic leukaemia surpasses 90% with contemporary therapy; however, patients remain burdened by the severe toxic effects of treatment, including asparaginase-associated pancreatitis. To investigate the risk of complications and risk of re......-exposing patients with asparaginase-associated pancreatitis to asparaginase, 18 acute lymphoblastic leukaemia trial groups merged data for this observational study. METHODS: Patient files from 26 trials run by 18 trial groups were reviewed on children (aged 1·0-17·9 years) diagnosed with t(9;22)-negative acute...... lymphoblastic leukaemia between June 1, 1996, and Jan 1, 2016, who within 50 days of asparaginase exposure developed asparaginase-associated pancreatitis. Asparaginase-associated pancreatitis was defined by at least two criteria: abdominal pain, pancreatic enzymes at least three times the upper limit of normal...

  7. Successful Control of Disseminated Intravascular Coagulation by Recombinant Thrombomodulin during Arsenic Trioxide Treatment in Relapsed Patient with Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Motohiro Shindo

    2012-01-01

    Full Text Available Disseminated intravascular coagulation (DIC frequently occurs in patients with acute promyelocytic leukemia (APL. With the induction of therapy in APL using all-trans retinoic acid (ATRA, DIC can be controlled in most cases as ATRA usually shows immediate improvement of the APL. However, arsenic trioxide (ATO which has been used for the treatment of relapse in APL patients has shown to take time to suppress APL cells, therefore the control of DIC in APL with ATO treatment is a major problem. Recently, the recombinant soluble thrombomodulin fragment has received a lot of attention as the novel drug for the treatment of DIC with high efficacy. Here, we present a relapsed patient with APL in whom DIC was successfully and safely controlled by rTM during treatment with ATO.

  8. Dietary management of acute diarrhoea in childhood.

    Science.gov (United States)

    Booth, I W

    1993-04-17

    Gastroenteritis in children is usually treated with the graded introduction of milk feeds after rehydration. Although having never been rigorously tested, the practice of gradually increasing milk strength over several days has been considered an appropriate means of warding against lactose intolerance and preventing sensitization to cow's milk antigens. These guidelines were formulated in Europe and North America and invariably lead to a reduction in nutrient intake. Malnourished children in developing countries, however, may experience an average 5-6 episodes of acute diarrhea per year and the nutrient effects are cumulative. A recent study from Latin America explored whether continued feeding is safe for infants under age 6 months and whether malnourished children respond adversely. Infants randomly assigned to receive full strength cow's milk immediately after rehydration did not have more treatment failures, higher stool outputs, or longer lasting diarrhea than those whose feeds were regarded to full strength over 48 hours. It is unclear, however, whether the youngest or more malnourished subjects were overrepresented in the treatment failures. Results also indicate that deciding to change treatment should not be dictated by the presence of reducing substances in the faeces; the majority of infants with reducing substances in their stools did well. This study offers the first scientific support for rapidly reintroducing full-strength milk formula after gastroenteritis is malnourished patients under 6 months of age. The 10% of infants in which dehydration recurs after reintroducing milk feeds are still difficult to manage. In the absence of yogurt or lactose-free formula, a locally-produced modular feed of chicken, starch, and vegetable oil may be suitable.

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

    International Nuclear Information System (INIS)

    Rossig, C.; Juergens, H.

    2008-01-01

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

  10. 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.

  11. Childhood acute lymphoblastic leukemia: from genome to patient

    International Nuclear Information System (INIS)

    Kolenova, A.

    2016-01-01

    Acute lymphoblastic leukemia is the most common malignant disease in childhood. During recent decades prognosis for children with acute leukemia has greatly improved, including the patients treated in the Slovak Republic. The prognosis for these patients has improved as a result of the systematic and well-organized international research efforts and clinical trials. The advent of new genomic technologies has provided new insights into leukemogenesis, identified many novel subtypes of leukemia, and triggered development of new therapeutic formulations. The success of treatment depends on stratifying patients into risk group and incorporating novel treatment strategies.The Slovak pediatric leukemia group is actively incorporated into these international clinical trials and the outcome for our patients is comparable to the results published in Western Europe. (author)

  12. Pre- and post-transplant minimal residual disease predicts relapse occurrence in children with acute lymphoblastic leukaemia.

    Science.gov (United States)

    Lovisa, Federica; Zecca, Marco; Rossi, Bartolomeo; Campeggio, Mimma; Magrin, Elisa; Giarin, Emanuela; Buldini, Barbara; Songia, Simona; Cazzaniga, Giovanni; Mina, Tommaso; Acquafredda, Gloria; Quarello, Paola; Locatelli, Franco; Fagioli, Franca; Basso, Giuseppe

    2018-03-01

    Relapse remains the leading cause of treatment failure in children with acute lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem cell transplantation (HSCT). We retrospectively investigated the prognostic role of minimal residual disease (MRD) before and after HSCT in 119 children transplanted in complete remission (CR). MRD was measured by polymerase chain reaction in bone marrow samples collected pre-HSCT and during the first and third trimesters after HSCT (post-HSCT1 and post-HSCT3). The overall event-free survival (EFS) was 50%. The cumulative incidence of relapse and non-relapse mortality was 41% and 9%. Any degree of detectable pre-HSCT MRD was associated with poor outcome: EFS was 39% and 18% in patients with MRD positivity <1 × 10 -3 and ≥1 × 10 -3 , respectively, versus 73% in MRD-negative patients (P < 0·001). This effect was maintained in different disease remissions, but low-level MRD had a very strong negative impact only in patients transplanted in second or further CR. Also, MRD after HSCT enabled patients to be stratified, with increasing MRD between post-HSCT1 and post-HSCT3 clearly defining cohorts with a different outcome. MRD is an important prognostic factor both before and after transplantation. Given that MRD persistence after HSCT is associated with dismal outcome, these patients could benefit from early discontinuation of immunosuppression, or pre-emptive immuno-therapy. © 2018 John Wiley & Sons Ltd.

  13. 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

  14. 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...... 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...

  15. 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

  16. A therapeutic trial of decitabine and vorinostat in combination with chemotherapy for relapsed/refractory acute lymphoblastic leukemia.

    Science.gov (United States)

    Burke, Michael J; Lamba, Jatinder K; Pounds, Stanley; Cao, Xueyuan; Ghodke-Puranik, Yogita; Lindgren, Bruce R; Weigel, Brenda J; Verneris, Michael R; Miller, Jeffrey S

    2014-09-01

    DNA hypermethylation and histone deacetylation are pathways of leukemia resistance. We investigated the tolerability and efficacy of decitabine and vorinostat plus chemotherapy in relapse/refractory acute lymphoblastic leukemia (ALL). Decitabine (15 mg/m(2) iv) and vorinostat (230 mg/m(2) PO div BID) were given days 1-4 followed by vincristine, prednisone, PEG-asparaginase, and doxorubicin. Genome wide methylation profiles were performed in 8 matched patient bone marrow (BM) samples taken at day 0 and day 5 (postdecitabine). The median age was 16 (range, 3-54) years. All patients had a prior BM relapse, with five relapsing after allogeneic transplant. The most common nonhematological toxicities possibly related to decitabine or vorinostat were infection with neutropenia (grade 3; n = 4) and fever/neutropenia (grade 3, n = 4; grade 4, n = 1). Of the 13 eligible patients, four achieved complete remission without platelet recovery (CRp), two partial response (PR), one stable disease (SD), one progressive disease (PD), two deaths on study and three patients who did not have end of therapy disease evaluations for an overall response rate of 46.2% (CRp + PR). Following decitabine, significant genome-wide hypo-methylation was observed. Comparison of clinical responders with nonresponders identified methylation profiles of clinical and biological relevance. Decitabine and vorinostat followed by re-Induction chemotherapy was tolerable and demonstrated clinical benefit in relapsed patients with ALL. Methylation differences were identified between responders and nonresponders indicating interpatient variation, which could impact clinical outcome. This study was registered at www.clinicaltrials.gov as NCT00882206. © 2014 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Eun-Jung Lee

    2012-03-01

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

  18. Gemtuzumab ozogamicin (Mylotarg) in children with refractory or relapsed acute myeloid leukemia.

    NARCIS (Netherlands)

    Reinhardt, D; Diekamp, S; Fleischhack, G; Corbacioglu, C; Jurgens, H; Dworzak, M; Kaspers, G.J.L.; Creutzig, U.; Zwaan, C.M.

    2004-01-01

    BACKGROUND: Gemtuzumab ozogamicin (GO) is an immunoconjugate consisting of the CD33 antibody and calicheamicin, a potent cytotoxic agent. Developed for targeted treatment of CD33-positive AML, studies in adults showed its efficacy in relapsed and refractory AML. PATIENTS AND METHOD: We report 12

  19. [Cytopathologic features of childhood acute leukemia at the Hospital de Especialidades Pediátricas, Chiapas, Mexico].

    Science.gov (United States)

    Lepe-Zúñiga, José Luis; Jerónimo-López, Francisco Javier; Hernández-Orantes, Jorge Gregorio

    Childhood acute leukemia cytological features are unknown in Chiapas, Mexico. Defining these features is important because this is a relatively isolated population with high consanguinity index, and these aspects could determine differences in responses to treatment and outcome. Eighty-one childhood acute leukemia cases treated at the Hospital de Especialidades Pediátricas in Chiapas were characterized by morphology, immunophenotype, genotype, initial risk assignment and status at the time of the study. The proportion of leukemic cell types found in this study was B cell, 75.3%; myeloid, 16%; T cell, 3.7% and NK 1.2%. In B cell leukemia, genetic alterations were present in 40.6% of cases and had a specific outcome regardless of initial risk assessment. Cases with MLL gene alteration died within a month from diagnosis. Translocations were present in 17.5% B cases; t(1;19) was present in those with a favorable outcome. The t(12;21) translocation was related to initial remission and midterm relapse and dead. Hyperdiploidy was present in 20% of B cell cases with good outcome. In 38.5%of myeloid cases were translocations and karyotypic abnormalities. Short-term outcome in this group has been poor; 69% have died or abandoned treatment in relapse from 15 days to 37 months after diagnosis. Relative frequency of different types of acute leukemia in patients treated at a tertiary level pediatric hospital in Chiapas, Mexico, was similar to the one found in other parts of the country. Patients' outcome, under a standardized treatment, differs according to the group, the subgroup and the presence and type of genetic alterations. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  20. The Total Body Irradiation Schedule Affects Acute Leukemia Relapse After Matched T Cell–Depleted Hematopoietic Stem Cell Transplantation

    International Nuclear Information System (INIS)

    Aristei, Cynthia; Carotti, Alessandra; Palazzari, Elisa; Amico, Lucia; Ruggeri, Loredana; Perrucci, Elisabetta; Falcinelli, Lorenzo; Lancellotta, Valentina; Palumbo, Isabella; Falzetti, Franca; Aversa, Franco; Merluzzi, Mara; Velardi, Andrea; Martelli, Massimo Fabrizio

    2016-01-01

    Purpose: We sought to determine whether the total body irradiation (TBI) schedule affected outcome in patients with acute leukemia in complete remission who received T cell–depleted allogeneic hematopoietic stem cell transplantation from HLA identical siblings. Methods and Materials: The study recruited 55 patients (median age, 48 years; age range, 20-66 years; 30 men and 25 women; 34 with acute myeloid leukemia and 21 with acute lymphoid leukemia). Hyperfractionated TBI (HTBI) (1.2 Gy thrice daily for 4 days [for a total dose of 14.4 Gy] from day −12 to day −9) was administered to 29 patients. Single-dose TBI (STBI) (8 Gy, at a median dose rate of 10.7 cGy/min on day −9) was given to 26 patients. Results: All patients achieved primary, sustained engraftment with full donor-type chimerism. At 10 years, the overall cumulative incidence of transplant-related mortality was 11% (SE, ±0.1%). It was 7% (SE, ±0.2%) after HTBI and 15% (SE, ±0.5%) after STBI (P=.3). The overall cumulative incidence of relapse was 33% (SE, ±0.5). It was 13% (SE, ±0.5%) after HTBI and 46% (SE, ±1%) after STBI (P=.02). The overall probability of disease-free survival (DFS) was 59% (SE, ±7%). It was 67% (SE, ±0.84%) after HTBI and 37% (SE, ±1.4%) after STBI (P=.01). Multivariate analyses showed the TBI schedule was the only risk factor that significantly affected relapse and DFS (P=.01 and P=.03, respectively). Conclusions: In patients with acute leukemia, HTBI is more efficacious than STBI in eradicating minimal residual disease after HLA-matched T cell–depleted hematopoietic stem cell transplantation, thus affecting DFS.

  1. The Total Body Irradiation Schedule Affects Acute Leukemia Relapse After Matched T Cell–Depleted Hematopoietic Stem Cell Transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Aristei, Cynthia, E-mail: cynthia.aristei@unipg.it [Radiation Oncology Section, Department of Surgery and Biomedical Sciences, University of Perugia and Perugia General Hospital, Perugia (Italy); Carotti, Alessandra [Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine, Perugia General Hospital and University, Perugia (Italy); Palazzari, Elisa [Radiation Oncology Section, University of Perugia, Perugia (Italy); Amico, Lucia; Ruggeri, Loredana [Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine, Perugia General Hospital and University, Perugia (Italy); Perrucci, Elisabetta; Falcinelli, Lorenzo [Radiation Oncology Division, Perugia General Hospital, Perugia (Italy); Lancellotta, Valentina [Radiation Oncology Section, University of Perugia, Perugia (Italy); Palumbo, Isabella [Radiation Oncology Section, Department of Surgery and Biomedical Sciences, University of Perugia and Perugia General Hospital, Perugia (Italy); Falzetti, Franca [Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine, Perugia General Hospital and University, Perugia (Italy); Aversa, Franco [Hematology and Bone Marrow Transplant Unit, Department of Clinical and Experimental Medicine, Parma General Hospital and University, Parma (Italy); Merluzzi, Mara; Velardi, Andrea; Martelli, Massimo Fabrizio [Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine, Perugia General Hospital and University, Perugia (Italy)

    2016-11-15

    Purpose: We sought to determine whether the total body irradiation (TBI) schedule affected outcome in patients with acute leukemia in complete remission who received T cell–depleted allogeneic hematopoietic stem cell transplantation from HLA identical siblings. Methods and Materials: The study recruited 55 patients (median age, 48 years; age range, 20-66 years; 30 men and 25 women; 34 with acute myeloid leukemia and 21 with acute lymphoid leukemia). Hyperfractionated TBI (HTBI) (1.2 Gy thrice daily for 4 days [for a total dose of 14.4 Gy] from day −12 to day −9) was administered to 29 patients. Single-dose TBI (STBI) (8 Gy, at a median dose rate of 10.7 cGy/min on day −9) was given to 26 patients. Results: All patients achieved primary, sustained engraftment with full donor-type chimerism. At 10 years, the overall cumulative incidence of transplant-related mortality was 11% (SE, ±0.1%). It was 7% (SE, ±0.2%) after HTBI and 15% (SE, ±0.5%) after STBI (P=.3). The overall cumulative incidence of relapse was 33% (SE, ±0.5). It was 13% (SE, ±0.5%) after HTBI and 46% (SE, ±1%) after STBI (P=.02). The overall probability of disease-free survival (DFS) was 59% (SE, ±7%). It was 67% (SE, ±0.84%) after HTBI and 37% (SE, ±1.4%) after STBI (P=.01). Multivariate analyses showed the TBI schedule was the only risk factor that significantly affected relapse and DFS (P=.01 and P=.03, respectively). Conclusions: In patients with acute leukemia, HTBI is more efficacious than STBI in eradicating minimal residual disease after HLA-matched T cell–depleted hematopoietic stem cell transplantation, thus affecting DFS.

  2. Profile of blinatumomab and its potential in the treatment of relapsed/refractory acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Ribera JM

    2015-06-01

    Full Text Available Josep-Maria Ribera, Albert Ferrer, Jordi Ribera, Eulàlia GenescàClinical Hematology Department, ICO-Hospital Germans Trias i Pujol, Josep Carreras Research Institute, Universitat Autònoma de Barcelona, Badalona, SpainAbstract: The CD19 marker is expressed on the surface of normal and malignant immature or mature B-cells. On the other hand, immunotherapy involving T-cells is a promising modality of treatment for many neoplastic diseases including leukemias and lymphomas. The CD19/CD3-bispecific T-cell-engaging (BiTE® monoclonal antibody blinatumomab can transiently engage cytotoxic T-cells to CD19+ target B-cells inducing serial perforin-mediated lysis. In the first clinical trial, blinatumomab showed efficacy in non-Hodgkin’s lymphomas, but the most important trials have been conducted in relapsed/refractory (R/R acute lymphoblastic leukemia (ALL and in ALL with minimal residual disease. Encouraging reports on the activity of blinatumomab in R/R Philadelphia chromosome-negative B-cell precursor ALL led to its approval by the US Food and Drug Administration on December 3, 2014 after an accelerated review process. This review focuses on the profile of blinatumomab and its activity in R/R ALL.Keywords: acute lymphoblastic leukemia, relapsed/refractory, BiTE® monoclonal antibodies, blinatumomab

  3. Influence of socioeconomic status on childhood acute lymphoblastic leukemia treatment in Indonesia.

    Science.gov (United States)

    Mostert, Saskia; Sitaresmi, Mei N; Gundy, Chad M; Sutaryo; Veerman, Anjo J P

    2006-12-01

    A major reason for poor survival of childhood acute lymphoblastic leukemia in developing countries is treatment refusal or abandonment. This can be associated with parental socioeconomic status and attitudes of health care providers. Our study examined the influence of 2 socioeconomic status determinants, parental income and education, on treatment in an Indonesian academic hospital. Medical charts of 164 patients who received a diagnosis of acute lymphoblastic leukemia between 1997 and 2002 were abstracted retrospectively. Data on treatment results and parental financial and educational background were collected. Open interviews were conducted with parents and health care providers. Of all patients, 35% refused or abandoned treatment, 23% experienced treatment-related death, 22% had progressive or relapsed leukemia, and 20% had an overall event-free survival. Treatment results differed significantly between patients with different socioeconomic status; 47% of poor and 2% of prosperous patients refused or abandoned treatment. Although poor and prosperous patients used the same protocol, the provided treatment differed. Poor patients received less individualized attention from oncologists and less structured parental education. Strong social hierarchical structures hindered communication with doctors, resulting in a lack of parental understanding of the necessity to continue treatment. Most poor patients could not afford treatment. Access to donated chemotherapy also was inadequate. Treatment refusal or abandonment frequently resulted. There was no follow-up system to detect and contact dropouts. Health care providers were not fully aware that their own attitude and communication skills were important for ensuring compliance of patients and parents. Children's survival of acute lymphoblastic leukemia in developing countries could improve if problems that are associated with parental financial and educational background and medical teams' attitudes to treatment and

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

    Science.gov (United States)

    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.

  5. Neuropsychological sequelae of central nervous system prophylaxis in survivors of childhood acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Said, J.A.; Waters, B.G.; Cousens, P.; Stevens, M.M.

    1989-01-01

    We assessed neuropsychologically 106 children with acute lymphoblastic leukemia (ALL) who had all received cranial irradiation for the prevention of central nervous system (CNS) leukemia 1-13 years previously. Children were assessed for adverse late effects of their therapy, using age-appropriate Wechsler measures of overall intellectual ability and supplementary tests. Forty-five siblings near in age to the patients were tested as controls. The patients who had had the most intensive central nervous system (CNS) prophylaxis were found to have a WISC-R Full Scale IQ 17 points lower than the sibling control group. Performance IQ was more affected than verbal IQ. The patients were more easily distracted and less able to concentrate. The severity of the aftereffects was related to younger age at the time of CNS prophylaxis and to a higher dose of cranial irradiation but not to time since CNS prophylaxis. CNS prophylaxis using a combination of cranial irradiation and intrathecal methotrexate has lowered the incidence of CNS relapse in childhood ALL but is associated with considerable long-term morbidity in survivors

  6. Diagnosis of central nervous system relapse of pediatric acute lymphoblastic leukemia: Impact of routine cytological CSF analysis at the time of intrathecal chemotherapy.

    Science.gov (United States)

    Gassas, Adam; Krueger, Joerg; Alvi, Saima; Sung, Lillian; Hitzler, Johanne; Lieberman, Lani

    2014-12-01

    Despite the success of central nervous system (CNS) directed therapy in pediatric acute lymphoblastic leukemia (ALL), relapse involving the CNS continues to be observed in 5-10% of children when utilizing standard intrathecal prophylactic chemotherapy. While most pediatric ALL treatment protocols mandate regular lumbar punctures (LP) for the intrathecal injection of chemotherapy, the value of routine cytological analysis of cerebrospinal fluid (CSF) during therapy is unknown. Our objective was to assess the diagnostic value of routine CSF analysis during ALL therapy. To allow for at least 10 years of follow up from ALL diagnosis, children (0-18 years) with ALL diagnosed and treated at SickKids, Toronto, Canada between 1994-2004 were studied. Medical records of patients with CNS relapse were examined to determine whether CNS relapse was diagnosed based on cytology of a routinely obtained CSF sample, a CSF sample obtained because of signs and symptoms or a CSF sample obtained after the diagnosis of a bone marrow relapse. Of 494 children treated for ALL, 31 (6.6%) developed a relapse of ALL involving the CNS. Twenty-two had an isolated CNS relapse and nine had a combined bone marrow and CNS relapse. Among patients with isolated CNS relapse, 73% (16/22) were diagnosed based on routine CSF samples obtained from asymptomatic children. Conversely, 89% (8/9) of children with combined bone marrow and CNS relapse presented with symptoms and signs that prompted CSF examination. Routine CSF examination at the time of LP for intrathecal chemotherapy is useful in detecting CNS relapse. © 2014 Wiley Periodicals, Inc.

  7. Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial.

    Science.gov (United States)

    Iijima, Kazumoto; Sako, Mayumi; Nozu, Kandai; Mori, Rintaro; Tuchida, Nao; Kamei, Koichi; Miura, Kenichiro; Aya, Kunihiko; Nakanishi, Koichi; Ohtomo, Yoshiyuki; Takahashi, Shori; Tanaka, Ryojiro; Kaito, Hiroshi; Nakamura, Hidefumi; Ishikura, Kenji; Ito, Shuichi; Ohashi, Yasuo

    2014-10-04

    Rituximab could be an effective treatment for childhood-onset, complicated, frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). We investigated the efficacy and safety of rituximab in patients with high disease activity. We did a multicentre, double-blind, randomised, placebo-controlled trial at nine centres in Japan. We screened patients aged 2 years or older experiencing a relapse of FRNS or SDNS, which had originally been diagnosed as nephrotic syndrome when aged 1-18 years. Patients with complicated FRNS or SDNS who met all other criteria were eligible for inclusion after remission of the relapse at screening. We used a computer-generated sequence to randomly assign patients (1:1) to receive rituximab (375 mg/m(2)) or placebo once weekly for 4 weeks, with age, institution, treatment history, and the intervals between the previous three relapses as adjustment factors. Patients, guardians, caregivers, physicians, and individuals assessing outcomes were masked to assignments. All patients received standard steroid treatment for the relapse at screening and stopped taking immunosuppressive agents by 169 days after randomisation. Patients were followed up for 1 year. The primary endpoint was the relapse-free period. Safety endpoints were frequency and severity of adverse events. Patients who received their assigned intervention were included in analyses. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000001405. Patients were centrally registered between Nov 13, 2008, and May 19, 2010. Of 52 patients who underwent randomisation, 48 received the assigned intervention (24 were given rituximab and 24 placebo). The median relapse-free period was significantly longer in the rituximab group (267 days, 95% CI 223-374) than in the placebo group (101 days, 70-155; hazard ratio: 0·27, 0·14-0·53; p<0·0001). Ten patients (42%) in the rituximab group and six (25

  8. 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

  9. 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

    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......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...... hyperdiploidy and t(12;21) ALL into 2 subgroups with different probability of relapse. By using supervised learning, we constructed multivariate classifiers by external cross-validation procedures. We identified 40 genes that consistently contributed to accurate discrimination between the main subtypes of BCP...

  10. 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...... ALL and gene sets that discriminated between subtypes of ALL and between ALL and controls in pairwise classification analyses. We also identified 20 individual genes with DNA methylation levels that predicted relapse of leukemia. Thus, methylation analysis should be explored as a method to improve...

  11. Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    von Stackelberg, Arend; Locatelli, Franco; Zugmaier, Gerhard; Handgretinger, Rupert; Trippett, Tanya M; Rizzari, Carmelo; Bader, Peter; O'Brien, Maureen M; Brethon, Benoît; Bhojwani, Deepa; Schlegel, Paul Gerhardt; Borkhardt, Arndt; Rheingold, Susan R; Cooper, Todd Michael; Zwaan, Christian M; Barnette, Phillip; Messina, Chiara; Michel, Gérard; DuBois, Steven G; Hu, Kuolung; Zhu, Min; Whitlock, James A; Gore, Lia

    2016-12-20

    Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II). Results We treated 49 patients in phase I and 44 patients in phase II. Four patients had dose-limiting toxicities in cycle 1 (phase I). Three experienced grade 4 cytokine-release syndrome (one attributed to grade 5 cardiac failure); one had fatal respiratory failure. The maximum-tolerated dosage was 15 µg/m 2 /d. Blinatumomab pharmacokinetics was linear across dosage levels and consistent among age groups. On the basis of the phase I data, the recommended blinatumomab dosage for children with relapsed/refractory ALL was 5 µg/m 2 /d for the first 7 days, followed by 15 µg/m 2 /d thereafter. Among the 70 patients who received the recommended dosage, 27 (39%; 95% CI, 27% to 51%) achieved complete remission within the first two cycles, 14 (52%) of whom achieved complete minimal residual disease response. The most frequent grade ≥ 3 adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%). Three patients (4%) and one patient (1%) had cytokine-release syndrome of grade 3 and 4, respectively. Two patients (3%) interrupted treatment after grade 2 seizures. Conclusion This trial, which to the best of our knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL. Blinatumomab may represent an important new treatment option in this setting, requiring further investigation in curative indications.

  12. Relapse Prevention in Major Depressive Disorder After Successful Acute Electroconvulsive Treatment

    DEFF Research Database (Denmark)

    Martiny, K; Larsen, E R; Licht, R W

    2015-01-01

    the study period, and one third completed. Discussion: Due to small sample size, no valid efficacy inferences could be made. The outcome was poor, probably due to tapering off of non-study psychotropic drugs after randomisation; this has implications for future study designs. ClinicalTrials.gov Identifier...... randomised (20% of the planned sample size). No statistically significant between-group differences could be detected. When all patients receiving escitalopram were compared with those receiving nortriptyline, a marginal superiority of nortriptyline was found (p=0.08). One third of patients relapsed during...

  13. Phase 1 study of clofarabine in pediatric patients with relapsed/refractory acute lymphoblastic leukemia in Japan.

    Science.gov (United States)

    Koh, Katsuyoshi; Ogawa, Chitose; Okamoto, Yasuhiro; Kudo, Kazuko; Inagaki, Jiro; Morimoto, Tsuyoshi; Mizukami, Hideya; Ecstein-Fraisse, Evelyne; Kikuta, Atsushi

    2016-08-01

    A phase 1 study was conducted to evaluate the safety, pharmacokinetics (PK), efficacy and pharmacogenetic characteristics of clofarabine in seven Japanese pediatric patients with relapsed/refractory acute lymphoblastic leukemia (ALL). Patients in Cohort 1 received clofarabine 30 mg/m(2)/day for 5 days, followed by 52 mg/m(2)/day for 5 days in subsequent cycles. Cohort 2 patients were consistently treated with 52 mg/m(2)/day for 5 days. No more than six cycles were performed. Every patient had at least one ≥Grade 3 adverse event (AE). AEs (≥Grade 3) related to clofarabine were anaemia, neutropenia, febrile neutropenia, thrombocytopenia, alanine aminotransferase increased, aspartate aminotransferase increased, haemoglobin decreased, and platelet (PLT) count decreased. C max and AUC of clofarabine increased in a dose-dependent fashion, but its elimination half-life (T 1/2) did not appear to be dependent on dose or duration of treatment. Clofarabine at 52 mg/m(2)/day shows similarly tolerable safety and PK profiles compared to those in previous studies. No complete remission (CR), CR without PLT recovery, or partial remission was observed. Since clofarabine is already used as a key drug for relapsed/refractory ALL patients in many countries, the efficacy of clofarabine in Japanese pediatric patients should be evaluated in larger study including more patients, such as by post-marketing surveillance.

  14. An effective modestly intensive re-induction regimen with bortezomib in relapsed or refractory paediatric acute lymphoblastic leukaemia.

    Science.gov (United States)

    Kaspers, Gertjan J L; Niewerth, Denise; Wilhelm, Bram A J; Scholte-van Houtem, Peggy; Lopez-Yurda, Marta; Berkhof, Johannes; Cloos, Jacqueline; de Haas, Valerie; Mathôt, Ron A; Attarbaschi, Andishe; Baruchel, André; de Bont, Eveline S; Fagioli, Franca; Rössig, Claudia; Klingebiel, Thomas; De Moerloose, Barbara; Nelken, Brigitte; Palumbo, Giuseppe; Reinhardt, Dirk; Rohrlich, Pierre-Simon; Simon, Pauline; von Stackelberg, Arend; Zwaan, Christian Michel

    2018-05-01

    This trial explored the efficacy of re-induction chemotherapy including bortezomib in paediatric relapsed/refractory acute lymphoblastic leukaemia. Patients were randomized 1:1 to bortezomib (1.3 mg/m 2 /dose) administered early or late to a dexamethasone and vincristine backbone. Both groups did not differ regarding peripheral blast count on day 8, the primary endpoint. After cycle 1, 8 of 25 (32%) patients achieved complete remission with incomplete blood count recovery, 7 (28%) a partial remission and 10 had treatment failure. Most common grade 3-4 toxicities were febrile neutropenia (31%) and pain (17%). Bortezomib was safely combined with vincristine. Bortezomib rarely penetrated the cerebrospinal fluid. © 2018 John Wiley & Sons Ltd.

  15. Expression profile and specific network features of the apoptotic machinery explain relapse of acute myeloid leukemia after chemotherapy

    International Nuclear Information System (INIS)

    Ragusa, Marco; Consoli, Carla; Camuglia, Maria Grazia; Di Pietro, Cinzia; Milone, Giuseppe; Purrello, Michele; Avola, Giuseppe; Angelica, Rosario; Barbagallo, Davide; Guglielmino, Maria Rosa; Duro, Laura R; Majorana, Alessandra; Statello, Luisa; Salito, Loredana

    2010-01-01

    According to the different sensitivity of their bone marrow CD34+ cells to in vitro treatment with Etoposide or Mafosfamide, Acute Myeloid Leukaemia (AML) patients in apparent complete remission (CR) after chemotherapy induction may be classified into three groups: (i) normally responsive; (ii) chemoresistant; (iii) highly chemosensitive. This inversely correlates with in vivo CD34+ mobilization and, interestingly, also with the prognosis of the disease: patients showing a good mobilizing activity are resistant to chemotherapy and subject to significantly higher rates of Minimal Residual Disease (MRD) and relapse than the others. Based on its known role in patients' response to chemotherapy, we hypothesized an involvement of the Apoptotic Machinery (AM) in these phenotypic features. To investigate the molecular bases of the differential chemosensitivity of bone marrow hematopoietic stem cells (HSC) in CR AML patients, and the relationship between chemosensitivity, mobilizing activity and relapse rates, we analyzed their AM expression profile by performing Real Time RT-PCR of 84 AM genes in CD34+ pools from the two extreme classes of patients (i.e., chemoresistant and highly chemosensitive), and compared them with normal controls. The AM expression profiles of patients highlighted features that could satisfactorily explain their in vitro chemoresponsive phenotype: specifically, in chemoresistant patients we detected up regulation of antiapoptotic BIRC genes and down regulation of proapoptotic APAF1, FAS, FASL, TNFRSF25. Interestingly, our analysis of the AM network showed that the dysregulated genes in these patients are characterized by high network centrality (i.e., high values of betweenness, closeness, radiality, stress) and high involvement in drug response. AM genes represent critical nodes for the proper execution of cell death following pharmacological induction in patients. We propose that their dysregulation (either due to inborn or de novo genomic

  16. Expression profile and specific network features of the apoptotic machinery explain relapse of acute myeloid leukemia after chemotherapy

    Directory of Open Access Journals (Sweden)

    Di Pietro Cinzia

    2010-07-01

    Full Text Available Abstract Background According to the different sensitivity of their bone marrow CD34+ cells to in vitro treatment with Etoposide or Mafosfamide, Acute Myeloid Leukaemia (AML patients in apparent complete remission (CR after chemotherapy induction may be classified into three groups: (i normally responsive; (ii chemoresistant; (iii highly chemosensitive. This inversely correlates with in vivo CD34+ mobilization and, interestingly, also with the prognosis of the disease: patients showing a good mobilizing activity are resistant to chemotherapy and subject to significantly higher rates of Minimal Residual Disease (MRD and relapse than the others. Based on its known role in patients' response to chemotherapy, we hypothesized an involvement of the Apoptotic Machinery (AM in these phenotypic features. Methods To investigate the molecular bases of the differential chemosensitivity of bone marrow hematopoietic stem cells (HSC in CR AML patients, and the relationship between chemosensitivity, mobilizing activity and relapse rates, we analyzed their AM expression profile by performing Real Time RT-PCR of 84 AM genes in CD34+ pools from the two extreme classes of patients (i.e., chemoresistant and highly chemosensitive, and compared them with normal controls. Results The AM expression profiles of patients highlighted features that could satisfactorily explain their in vitro chemoresponsive phenotype: specifically, in chemoresistant patients we detected up regulation of antiapoptotic BIRC genes and down regulation of proapoptotic APAF1, FAS, FASL, TNFRSF25. Interestingly, our analysis of the AM network showed that the dysregulated genes in these patients are characterized by high network centrality (i.e., high values of betweenness, closeness, radiality, stress and high involvement in drug response. Conclusions AM genes represent critical nodes for the proper execution of cell death following pharmacological induction in patients. We propose that their

  17. Acute intrascrotal pathology in childhood: color Doppler study

    International Nuclear Information System (INIS)

    Cinta Sanguesa, C.; Muro, D.; Cortina, H.; Moreno, A.

    1997-01-01

    To asses the utility of color Doppler ultrasound in the study of acute intrascrotal pathology in childhood. Seventy-five boys with evidence of an acute intrascrotal abnormality were studied by means of color Doppler ultrasound. A 7.5 MHz linear transducer was used. The most common findings was inflammatory disease (60%) which was indicated by the presence of hyperemia in color Doppler. Of the nine boys with testicular torsion (12%) two presented extravaginal torsion, with a complete absence of intratesticular vascularization. Intravaginal torsion was observed in seven patients, six of whom presented reduced vascularization in the abnormal testicle with respect to the healthy testicle. There was one false negative in which testicular vascularization was normal but 360 degree centigree torsion was found at surgery. In addition, there were seven cases of hydatid torsion (9.33%), four of idiopathic scrotal swelling (5.3%). two cases of intermittent torsion (2.6%) and one case of Shcolein-Henoch purpura (1.3%). The ultrasound findings were completely nornal in seven boys. Color Doppler is a rapid, noninvasive method for assessing testicular blood flow. The elevated sensitivity and specificity (85.7 and 100%, respectively, in our series) for testicular torsion make Doppler ultrasound a highly reliable method for the study of this disorder. (Author) 18 refs

  18. Impact of cytomegalovirus reactivation on relapse and survival in patients with acute leukemia who received allogeneic hematopoietic stem cell transplantation in first remission

    OpenAIRE

    Yoon, Jae-Ho; Lee, Seok; Kim, Hee-Je; Jeon, Young-Woo; Lee, Sung-Eun; Cho, Byung-Sik; Lee, Dong-Gun; Eom, Ki-Seong; Kim, Yoo-Jin; Min, Chang-Ki; Cho, Seok-Goo; Min, Woo-Sung; Lee, Jong Wook

    2016-01-01

    Cytomegalovirus (CMV)-reactivation is associated with graft-vs-leukemia (GVL) effect by stimulating natural-killer or T-cells, which showed leukemia relapse prevention after hematopoietic stem cell transplantation (HSCT). We enrolled patients with acute myeloid leukemia (n = 197) and acute lymphoid leukemia (n = 192) who underwent allogeneic-HSCT in first remission. We measured RQ-PCR weekly to detect CMV-reactivation and preemptively used ganciclovir (GCV) when the titer increased twice cons...

  19. Fetal Growth and Childhood Acute Lymphoblastic Leukemia: Findings from the Childhood Leukemia International Consortium (CLIC)

    Science.gov (United States)

    Milne, Elizabeth; Greenop, Kathryn R.; Metayer, Catherine; Schüz, Joachim; Petridou, Eleni; Pombo-de-Oliveira, Maria S.; Infante-Rivard, Claire; Roman, Eve; Dockerty, John D.; Spector, Logan G.; Koifman, Sérgio; Orsi, Laurent; Rudant, Jérémie; Dessypris, Nick; Simpson, Jill; Lightfoot, Tracy; Kaatsch, Peter; Baka, Margarita; Faro, Alessandra; Armstrong, Bruce K.; Clavel, Jacqueline; Buffler, Patricia A.

    2013-01-01

    Positive associations have been reported between measures of accelerated fetal growth and risk of childhood acute lymphoblastic leukemia (ALL). We investigated this association by pooling individual-level data from 12 case-control studies participating in the Childhood Leukemia International Consortium. Two measures of fetal growth – weight-for-gestational-age and proportion of optimal birth weight (POBW) – were analysed. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, and combined in fixed effects meta-analyses. Pooled analyses of all data were also undertaken using multivariable logistic regression. Subgroup analyses were undertaken when possible. Data on weight for gestational age were available for 7,348 cases and 12,489 controls from all 12 studies and POBW data were available for 1,680 cases and 3,139 controls from three studies. The summary ORs from the meta-analyses were 1.24 (95% CI 1.13, 1.36) for children who were large for gestational age relative to appropriate for gestational age, and 1.16 (95% CI: 1.09, 1.24) for a one standard deviation increase in POBW. The pooled analyses produced similar results. The summary and pooled ORs for small-for-gestational-age children were 0.83 (95% CI: 0.75, 0.92) and 0.86 (95% CI 0.77, 0.95) respectively. Results were consistent across subgroups defined by sex, ethnicity and immunophenotype, and when the analysis was restricted to children who did not have high birth weight. The evidence that accelerated fetal growth is associated with a modest increased risk of childhood ALL is strong and consistent with known biological mechanisms involving insulin like growth factors. PMID:23754574

  20. Childhood Acute Lymphoblastic Leukemia and Indicators of Early Immune Stimulation: A Childhood Leukemia International Consortium Study

    Science.gov (United States)

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

    2015-01-01

    The associations between childhood acute lymphoblastic leukemia (ALL) and several proxies of early stimulation of the immune system, that is, day-care center attendance, birth order, maternally reported common infections in infancy, and breastfeeding, were investigated by using data from 11 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980–2010). The sample included 7,399 ALL cases and 11,181 controls aged 2–14 years. The data were collected by questionnaires administered to the parents. Pooled odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Day-care center attendance in the first year of life was associated with a reduced risk of ALL (odds ratio = 0.77, 95% confidence interval: 0.71, 0.84), with a marked inverse trend with earlier age at start (P < 0.0001). An inverse association was also observed with breastfeeding duration of 6 months or more (odds ratio = 0.86, 95% confidence interval: 0.79, 0.94). No significant relationship with a history of common infections in infancy was observed even though the odds ratio was less than 1 for more than 3 infections. The findings of this large pooled analysis reinforce the hypothesis that day-care center attendance in infancy and prolonged breastfeeding are associated with a decreased risk of ALL. PMID:25731888

  1. 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

    2010-04-01

    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. 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. 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%). 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.

  2. Cardiac function in survivors of childhood acute myeloid leukemia treated with chemotherapy only

    DEFF Research Database (Denmark)

    Jarfelt, Marianne; Andersen, Niels Holmark; Glosli, Heidi

    2015-01-01

    OBJECTIVES: We report cardiac function of patients treated for Childhood acute myeloid leukemia with chemotherapy only according to three consecutive Nordic protocols. METHODS: Ninety-eight of 138 eligible patients accepted examination with standardized echocardiography. Results were compared...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    Objectives: To investigate association of host genomic variation and risk of infections during treatment for childhood acute lymphoblastic leukaemia (ALL). Methods: We explored association of 34 000 singlenucleotide polymorphisms (SNPs) related primarily to pharmacogenomics and immune function...

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

    International Nuclear Information System (INIS)

    Kato, Yasuhiro; Ohno, Norioki; Horikawa, Yoko; Nishimura, Shin-ichiro; Ueda, Kazuhiro; Shimose, Shoji

    2002-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-12-01

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

  6. DNA methylation for subtype classification and prediction of treatment outcome in patients with childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Milani, Lili; Lundmark, Anders; Kiialainen, Anna; Nordlund, Jessica; Flaegstad, Trond; Forestier, Erik; Heyman, Mats; Jonmundsson, Gudmundur; Kanerva, Jukka; Schmiegelow, Kjeld; Söderhäll, Stefan; Gustafsson, Mats G; Lönnerholm, Gudmar; Syvänen, Ann-Christine

    2010-02-11

    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 hyperdiploidy and t(12;21) ALL into 2 subgroups with different probability of relapse. By using supervised learning, we constructed multivariate classifiers by external cross-validation procedures. We identified 40 genes that consistently contributed to accurate discrimination between the main subtypes of BCP ALL and gene sets that discriminated between subtypes of ALL and between ALL and controls in pairwise classification analyses. We also identified 20 individual genes with DNA methylation levels that predicted relapse of leukemia. Thus, methylation analysis should be explored as a method to improve stratification of ALL patients. The genes highlighted in our study are not enriched to specific pathways, but the gene expression levels are inversely correlated to the methylation levels.

  7. 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...

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

    Directory of Open Access Journals (Sweden)

    W. Y. Lim

    2015-01-01

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

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

    Science.gov (United States)

    Lim, W Y; Care, R; Lau, M; Chiruka, S; Dawes, P J D

    2015-01-01

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

  10. Childhood acute bacterial meningitis: clinical spectrum, bacteriological profile and outcome

    International Nuclear Information System (INIS)

    Bari, A.; Zeeshan, S.; Rathore, A. W.

    2016-01-01

    Objective: To determine the disease pattern, etiological agents and outcome of childhood acute bacterial meningitis. Study Design: A descriptive study. Place and Duration of Study: Department of Paediatric Medicine, The Children's Hospital, Lahore, from January to December 2012. Methodology: A total of 199 children between the ages of 1 month and 5 years, admitted with the diagnosis of meningitis on the basis of clinical findings and positive cerebrospinal fluid (CSF), were included. In all patients, complete blood count (CBC), CSF culture sensitivity, and blood culture sensitivity were performed. Data was analysed using SPSS version 20. Results: Out of 199 children, 127 (63.8%) were males with M:F ratio of 1.7:1. Mean age was 11.33 ± 12 months. Maximum numbers of children were < 1 year of age, 136 (68.3%). Only 90 (45.2%) children were fully vaccinated according to Expanded Program of Immunisation (EPI) schedule. Presentations with refusal to take feed (p=0.008) and with impaired conscious state were independent predictors of death (p=0.002). Complications were noted in 34 (17%) and were significantly associated with severe malnutrition (p=0.006) and altered conscious level at presentation (p < 0.001). The common pathogens identified on CSF culture were coagulase negative staphylococci (CoNS) in 11 (5.5%) and streptococcus pneumoniae in 5 (2.5%). Overall mortality was 10.1%. The commonest pathogen isolated from children who died was streptococcus pneumoniae (p=0.039). Conclusion: Acute bacterial meningitis mostly affected children under the age of 1 year. CSF culture revealed both Gram-positive and Gram-negative bacteria. The most common pathogen in children who died was streptococcus pneumoniae. (author)

  11. 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

  12. E2F3a gene expression has prognostic significance in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Wang, Kai-Ling; Mei, Yan-Yan; Cui, Lei; Zhao, Xiao-Xi; Li, Wei-Jing; Gao, Chao; Liu, Shu-Guang; Jiao, Ying; Liu, Fei-Fei; Wu, Min-Yuan; Ding, Wei; Li, Zhi-Gang

    2014-10-01

    To study E2F3a expression and its clinical significance in children with acute lymphoblastic leukemia (ALL). We quantified E2F3a expression at diagnosis in 148 children with ALL by real-time PCR. In the test cohort (n = 48), receiver operating characteristic (ROC) curve was used to find the best cut-off point to divide the patients into E2F3a low- and high-expression groups. The prognostic significance of E2F3a expression was investigated in the test cohort and confirmed in the validation cohort (n = 100). The correlations of E2F3a expression with the clinical features and treatment outcome of these patients were analyzed. ROC curve analysis indicated that the best cut-off point of E2F3a expression was 0.3780. In the test cohort, leukemia-free survival (LFS) and event-free survival (EFS) of the low-expression group were lower than those of the high-expression group (log rank: P = 0.026 for both). This finding was verified in the validation cohort. LFS, EFS, and overall survival were also lower in the low-expression group than in the high-expression group (log rank, P = 0.015, 0.008, and 0.002 respectively). E2F3a low expression was correlated with the existence of BCR-ABL fusion. An algorithm composed of E2F3a expression and minimal residual disease (MRD) could predict relapse or induction failure more precisely than current risk stratification. These results were still significant in the ALL patients without BCR-ABL fusion. Low expression of E2F3a was associated with inferior prognosis in childhood ALL. An algorithm composed of E2F3a expression and MRD could predict relapse or induction failure more precisely than that of the current risk stratification. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Unilateral optic disk edema with central retinal artery and vein occlusions as the presenting signs of relapse in acute lymphoblastic leukemia.

    Science.gov (United States)

    Salazar Méndez, R; Fonollá Gil, M

    2014-11-01

    A 39-year-old man with Philadelphia chromosome-positive acute lymphoblastic leukemia (LAL Ph+) developed progressive vision loss to no light perception in his right eye. He had optic disk edema and later developed central artery and vein occlusions. Pan-photocoagulation, as well as radiotherapy of the whole brain were performed in several fractions. Unfortunately the patient died of hematological relapse 4 months later. Optic nerve infiltration may appear as an isolated sign of a leukemia relapse, even before a hematological relapse occurs. Leukemic optic neuropathy is a critical sign, not only for vision, but also for life, and radiotherapy should be immediately performed before irreversible optic nerve damage occurs. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  14. 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

  15. Childhood Acute Myeloid Leukemia Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Acute myeloid leukemia (AML), juvenile myelomonocytic leukemia (JMML), acute promyelocytic leukemia (APL) and chronic myeloid leukemia (CML) account for about 20% of childhood myeloid leukemias. Other myeloid malignancies include transient abnormal myelopoiesis and myelodysplastic syndrome. Get detailed information about the classification, clinical presentation, diagnostic and molecular evaluation, prognosis, and treatment of newly diagnosed and recurrent disease in this summary for clinicians.

  16. Allogeneic stem cell transplantation in children with acute lymphoblastic leukemia after isolated central nervous system relapse: our experiences and review of the literature.

    Science.gov (United States)

    Yoshihara, T; Morimoto, A; Kuroda, H; Imamura, T; Ishida, H; Tsunamoto, K; Naya, M; Hibi, S; Todo, S; Imashuku, S

    2006-01-01

    The prognosis of patients with acute lymphoblastic leukemia (ALL) and central nervous system (CNS) relapse has historically been very poor. Although chemo-radiotherapy has improved outcomes, some patients still have a poor prognosis after CNS relapse. Therefore, allogeneic hematopoietic stem cell transplantation (allo-SCT) has recently become an option for treatment of CNS leukemia; however, information, particularly on the long-term outcome of transplant recipients, is limited. We performed allo-SCT in eight pediatric patients with ALL (n=7) or T-cell type non-Hodgkin's lymphoma (n=1), who had isolated CNS relapse. All patients survived for a median of 70.5 (range, 13-153) months after SCT. Sequelae developed late in some patients: mental retardation (IQ=47) in one patient, severe alopecia in two patients, limited chronic graft-versus-host-disease in three patients, and amenorrhea and/or hypothyroidism in three patients. Except for a pre-school child with post transplant CNS relapse, six out of seven patients show normal school/social performance. Our results clearly indicate a high cure rate of isolated CNS relapse by allo-SCT in pediatric lymphoid malignancies; however, there needs to be further studies to determine which are the appropriate candidates for transplantation and what is the best transplant regimen to achieve high cure rate and maintain good quality of life.

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

    Directory of Open Access Journals (Sweden)

    Denise Niewerth

    2016-09-01

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

  18. CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Davila, Marco L; Brentjens, Renier J

    2016-10-01

    Immunotherapy has demonstrated significant potential for the treatment of patients with chemotherapy-resistant hematologic malignancies and solid tumors. One type of immunotherapy involves the adoptive transfer of T cells that have been genetically modified with a chimeric antigen receptor (CAR) to target a tumor. These hybrid proteins are composed of the antigen-binding domains of an antibody fused to T-cell receptor signaling machinery. CAR T cells that target CD19 recently have made the jump from the laboratory to the clinic, and the results have been remarkable. CD19-targeted CAR T cells have induced complete remissions of disease in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), who have an expected complete response rate of 30% in response to chemotherapy. The high efficacy of CAR T cells in B-ALL suggests that regulatory approval of this therapy for this routinely fatal leukemia is on the horizon. We review the preclinical development of CAR T cells and their early clinical application for lymphoma. We also provide a comprehensive analysis of the use of CAR T cells in patients with B-ALL. In addition, we discuss the unique toxicities associated with this therapy and the management schemes that have been developed.

  19. Premature atherosclerosis after treatment for acute lymphoblastic leukemia in childhood

    Directory of Open Access Journals (Sweden)

    Elżbieta Sadurska

    2018-03-01

    Survivors of childhood ALL in the examined group demonstrated elevated concentrations of selected new biomarkers and increased IMT values, compared to controls, which may confirm the occurrence of endothelial injuries in blood vessels. This study indicates that subjects treated for childhood malignancy are at a higher risk of prematurely developing atherosclerosis.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: Previous studies have indicated that patients with thiopurine methyltransferase (TPMT) low activity (TPMT(LA)) have reduced risk of relapse but increased risk of second malignant neoplasm (SMN) compared to patients with TPMT wild-type (TPMT(WT)) when treated with 6 MP maintenance ther...

  1. Enhancing Brain Lesions during Acute Optic Neuritis and/or Longitudinally Extensive Transverse Myelitis May Portend a Higher Relapse Rate in Neuromyelitis Optica Spectrum Disorders.

    Science.gov (United States)

    Orman, G; Wang, K Y; Pekcevik, Y; Thompson, C B; Mealy, M; Levy, M; Izbudak, I

    2017-05-01

    Neuromyelitis optica spectrum disorders are inflammatory demyelinating disorders with optic neuritis and/or longitudinally extensive transverse myelitis episodes. We now know that neuromyelitis optica spectrum disorders are associated with antibodies to aquaporin-4, which are highly concentrated on astrocytic end-feet at the blood-brain barrier. Immune-mediated disruption of the blood-brain barrier may manifest as contrast enhancement on brain MR imaging. We aimed to delineate the extent and frequency of contrast enhancement on brain MR imaging within 1 month of optic neuritis and/or longitudinally extensive transverse myelitis attacks and to correlate contrast enhancement with outcome measures. Brain MRIs of patients with neuromyelitis optica spectrum disorders were evaluated for patterns of contrast enhancement (periependymal, cloudlike, leptomeningeal, and so forth). The Fisher exact test was used to evaluate differences between the proportion of contrast enhancement in patients who were seropositive and seronegative for aquaporin-4 antibodies. The Mann-Whitney test was used to compare the annualized relapse rate and disease duration between patients with and without contrast enhancement and with and without seropositivity. Brain MRIs of 77 patients were evaluated; 59 patients (10 males, 49 females) were scanned within 1 month of optic neuritis and/or longitudinally extensive transverse myelitis attacks and were included in the analysis. Forty-eight patients were seropositive, 9 were seronegative, and 2 were not tested for aquaporin-4 antibodies. Having brain contrast enhancement of any type during an acute attack was significantly associated with higher annualized relapse rates ( P = .03) and marginally associated with shorter disease duration ( P = .05). Having periependymal contrast enhancement was significantly associated with higher annualized relapse rates ( P = .03). Brain MRIs of patients with neuromyelitis optica spectrum disorders with contrast

  2. Genomic profiling of pediatric acute myeloid leukemia reveals a changing mutational landscape from disease diagnosis to relapse | Office of Cancer Genomics

    Science.gov (United States)

    The genomic and clinical information used to develop and implement therapeutic approaches for AML originated primarily from adult patients and has been generalized to patients with pediatric AML. However, age-specific molecular alterations are becoming more evident and may signify the need to age-stratify treatment regimens. The NCI/COG TARGET-AML initiative employed whole exome capture sequencing (WXS) to interrogate the genomic landscape of matched trios representing specimens collected upon diagnosis, remission, and relapse from 20 cases of de novo childhood AML.

  3. Monitoring minimal residual disease in children with high-risk relapses of acute lymphoblastic leukemia: prognostic relevance of early and late assessment.

    Science.gov (United States)

    Eckert, C; Hagedorn, N; Sramkova, L; Mann, G; Panzer-Grümayer, R; Peters, C; Bourquin, J-P; Klingebiel, T; Borkhardt, A; Cario, G; Alten, J; Escherich, G; Astrahantseff, K; Seeger, K; Henze, G; von Stackelberg, A

    2015-08-01

    The prognosis for children with high-risk relapsed acute lymphoblastic leukemia (ALL) is poor. Here, we assessed the prognostic importance of response during induction and consolidation treatment prior to hematopoietic stem cell transplantation (HSCT) aiming to evaluate the best time to assess minimal residual disease (MRD) for intervention strategies and in future trials in high-risk ALL relapse patients. Included patients (n=125) were treated uniformly according to the ALL-REZ BFM (Berlin-Frankfurt-Münster) 2002 relapse trial (median follow-up time=4.8 years). Patients with MRD ⩾10(-3) after induction treatment (76/119, 64%) or immediately preceding HSCT (19/71, 27%) had a significantly worse probability of disease-free survival 10 years after relapse treatment begin, with 26% (±6%) or 23% (±7%), respectively, compared with 58% (±8%) or 48% (±7%) for patients with MRD treatment reduced MRD to treatment can be used to quantify the activity of different induction treatment strategies in phase II trials. MRD persistence at ⩾10(-3) before HSCT reflects a disease highly resistant to conventional intensive chemotherapy and requiring prospective controlled investigation of new treatment strategies and drugs.

  4. Prolonged Survival of a Refractory Acute Myeloid Leukemia Patient after a Third Hematopoietic Stem Cell Transplantation with Umbilical Cord Blood following a Second Relapse

    Directory of Open Access Journals (Sweden)

    Suk-young Lee

    2014-01-01

    Full Text Available Although hematopoietic stem cell transplantation (HSCT has been considered to be the only way for potential cure of relapsed acute myeloid leukemia (AML, there has been no report on a third HSCT in patients with multiple relapsed AML. Here, we report a case of 53-year-old female who received a successful third allogeneic HSCT after relapse of AML following a second allogeneic HSCT. She was treated with a toxicity reduced conditioning regimen and received direct intrabone cord blood transplantation (CBT using a single unit of 5/6 HLA-matched cord blood as a graft source. Graft-versus-host disease prophylaxis was performed with a single agent of tacrolimus to increase graft-versus-leukemia effect. She is in remission for 8 months since the direct intrabone CBT. This report highlights not only the importance of individually adjusted approach but also the need for further investigation on the role of HSCT as a treatment modality in patients with refractory or multiple relapsed AML.

  5. HLA-DPβ1 Asp84-Lys69 antigen-binding signature predicts event-free survival in childhood B-cell precursor acute lymphoblastic leukaemia: results from the MRC UKALL XI childhood ALL trial.

    Science.gov (United States)

    Taylor, G M; Wade, R; Hussain, A; Thompson, P; Hann, I; Gibson, B; Eden, T; Richards, S

    2012-07-01

    We previously reported that children in the UKALL XI ALL trial with HLA-DP 1 and -DP 3 supertypes had significantly worse event-free survival (EFS) than children with other DP supertypes. As DP 1 and DP 3 share two of four key antigen-binding amino-acid polymorphisms (aspartic acid84-lysine69), we asked whether Asp84-Lys69 or Asp84 alone were independent prognostic indicators in childhood acute lymphoblastic leukemia (ALL). We analysed EFS in 798 UKALL XI patients, stratified by Asp84-Lys69 vs non-Asp84-Lys69, for a median follow-up of 12.5 years. Asp84-Lys69 was associated with a significantly worse EFS than non-Asp84-Lys69 (5-year EFS: Asp84-Lys69: 58.8% (95% CI (confidence of interval): 52.7-64.9%); non-Asp84-Lys69: 67.3% (63.4-71.2%); 2P=0.007). Post-relapse EFS was 10% less in Asp84-Lys69 than non-Asp84-Lys69 patients. EFS was significantly worse (P=0.03) and post-relapse EFS marginally worse (P=0.06) in patients with Asp84 compared with Gly84. These results suggest that Asp84-Lys69 predicted adverse EFS in the context of UKALL XI because of Asp84, and may have influenced post-relapse EFS. We speculate that this may be due to the recruitment of Asp84-Lys69-restricted regulatory T cells in the context of this regimen, leading to the re-emergence of residual disease. However, functional and molecular studies of the prognostic value of this and other HLA molecular signatures in other childhood ALL trials are needed.

  6. Childhood acute lower respiratory tract infections in Northern Nigeria

    African Journals Online (AJOL)

    2015-03-02

    Mar 2, 2015 ... cause of childhood morbidity and deaths worldwide1, 2. Of the estimated 7.6 ... years of age with community-acquired pneumonia. (CAP) would require ..... mon respiratory pathogens, such as Haemophilus influ- enzae and ...

  7. Brain hypothermia therapy for childhood acute encephalopathy based on clinical evidence

    OpenAIRE

    IMATAKA, GEORGE; ARISAKA, OSAMU

    2015-01-01

    Although previous studies have reported on the effectiveness of brain hypothermia therapy in childhood acute encephalopathy, additional studies in this field are necessary. In this review, we discussed brain hypothermia therapy methods for two clinical conditions for which sufficient evidences are currently available in the literature. The first condition is known as hypoxic-ischemic encephalopathy and occurs in newborns and the second condition is acute encephalopathy which occurs in adults ...

  8. Flow cytometric minimal residual disease assessment of peripheral blood in acute lymphoblastic leukaemia patients has potential for early detection of relapsed extramedullary disease.

    Science.gov (United States)

    Keegan, Alissa; Charest, Karry; Schmidt, Ryan; Briggs, Debra; Deangelo, Daniel J; Li, Betty; Morgan, Elizabeth A; Pozdnyakova, Olga

    2018-03-27

    To evaluate peripheral blood (PB) for minimal residual disease (MRD) assessment in adults with acute lymphoblastic leukaemia (ALL). We analysed 76 matched bone marrow (BM) aspirate and PB specimens independently for the presence of ALL MRD by six-colour flow cytometry (FC). The overall rate of BM MRD-positivity was 24% (18/76) and PB was also MRD-positive in 22% (4/18) of BM-positive cases. We identified two cases with evidence of leukaemic cells in PB at the time of the extramedullary relapse that were interpreted as MRD-negative in BM. The use of PB MRD as a non-invasive method for monitoring of systemic relapse may have added clinical and diagnostic value in patients with high risk of extramedullary disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

    Science.gov (United States)

    2016-01-01

    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. 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. 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 the budget-impact analysis, the

  10. 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

  11. Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2017-06-27

    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 Del(5q); 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); Recurrent Adult Acute Myeloid Leukemia

  12. 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.

  13. 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...

  14. 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

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

    NARCIS (Netherlands)

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

    1998-01-01

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

  16. Inotuzumab ozogamicin in adults with relapsed or refractory CD22-positive acute lymphoblastic leukemia: a phase 1/2 study.

    Science.gov (United States)

    DeAngelo, Daniel J; Stock, Wendy; Stein, Anthony S; Shustov, Andrei; Liedtke, Michaela; Schiffer, Charles A; Vandendries, Erik; Liau, Katherine; Ananthakrishnan, Revathi; Boni, Joseph; Laird, A Douglas; Fostvedt, Luke; Kantarjian, Hagop M; Advani, Anjali S

    2017-06-27

    This study evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of inotuzumab ozogamicin (InO) for CD22-positive relapsed/refractory acute lymphoblastic leukemia. In phase 1, patients received InO 1.2 (n = 3), 1.6 (n = 12), or 1.8 (n = 9) mg/m 2 per cycle on days 1, 8, and 15 over a 28-day cycle (≤6 cycles). The recommended phase 2 dose (RP2D) was confirmed (expansion cohort; n = 13); safety and activity of InO were assessed in patients receiving the RP2D in phase 2 (n = 35) and in all treated patients (n = 72). The RP2D was 1.8 mg/m 2 per cycle (0.8 mg/m 2 on day 1; 0.5 mg/m 2 on days 8 and 15), with reduction to 1.6 mg/m 2 per cycle after complete remission (CR) or CR with incomplete marrow recovery (CRi). Treatment-related toxicities were primarily cytopenias. Four patients experienced treatment-related venoocclusive disease/sinusoidal obstruction syndrome (VOD/SOS; 1 fatal). Two VOD/SOS events occurred during treatment without intervening transplant; of 24 patients proceeding to poststudy transplant, 2 experienced VOD/SOS after transplant. Forty-nine (68%) patients had CR/CRi, with 41 (84%) achieving minimal residual disease (MRD) negativity. Median progression-free survival was 3.9 (95% confidence interval, 2.9-5.4) months; median overall survival was 7.4 (5.7-9.2) months for all treated patients, with median 23.7 (range, 6.8-29.8) months of follow-up for all treated patients alive at data cutoff. Achievement of MRD negativity was associated with higher InO exposure. InO was well tolerated and demonstrated high single-agent activity and MRD-negativity rates. This trial was registered at www.clinicaltrials.gov as #NCT01363297.

  17. Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood

    NARCIS (Netherlands)

    Zeharia, Avraham; Shaag, Avraham; Houtkooper, Riekelt H.; Hindi, Tareq; de Lonlay, Pascale; Erez, Gilli; Hubert, Laurence; Saada, Ann; de Keyzer, Yves; Eshel, Gideon; Vaz, Frédéric M.; Pines, Ophry; Elpeleg, Orly

    2008-01-01

    Recurrent episodes of life-threatening myoglobinuria in childhood are caused by inborn errors of glycogenolysis, mitochondrial fatty acid beta-oxidation, and oxidative phosphorylation. Nonetheless, approximately half of the patients do not suffer from a defect in any of these pathways. Using

  18. Quantitative assessments of indoor air pollution and the risk of childhood acute leukemia in Shanghai

    International Nuclear Information System (INIS)

    Gao, Yu; Zhang, Yan; Kamijima, Michihiro; Sakai, Kiyoshi; Khalequzzaman, Md; Nakajima, Tamie; Shi, Rong; Wang, Xiaojin; Chen, Didi; Ji, Xiaofan; Han, Kaiyi; Tian, Ying

    2014-01-01

    We investigated the association between indoor air pollutants and childhood acute leukemia (AL). A total of 105 newly diagnosed cases and 105 1:1 gender-, age-, and hospital-matched controls were included. Measurements of indoor pollutants (including nitrogen dioxide (NO 2 ) and 17 types of volatile organic compounds (VOCs)) were taken with diffusive samplers for 64 pairs of cases and controls. Higher concentrations of NO 2 and almost half of VOCs were observed in the cases than in the controls and were associated with the increased risk of childhood AL. The use of synthetic materials for wall decoration and furniture in bedroom was related to the risk of childhood AL. Renovating the house in the last 5 years, changing furniture in the last 5 years, closing the doors and windows overnight in the winter and/or summer, paternal smoking history and outdoor pollutants affected VOC concentrations. Our results support the association between childhood AL and indoor air pollution. - Highlights: • We firstly assessed the effects of indoor air pollution on childhood AL in China. • Indoor air pollutants were assessed by questionnaire and quantitative measurements. • NO 2 and 17 types of VOCs were measured in bedrooms of both cases and controls. • Higher concentrations of indoor air pollutants increased the risk of childhood AL. • Indoor behavioral factors and outdoor pollution might affect indoor air pollution. - Higher concentrations of indoor air pollutants were related to an elevated risk of childhood AL

  19. [Relapse: causes and consequences].

    Science.gov (United States)

    Thomas, P

    2013-09-01

    Relapse after a first episode of schizophrenia is the recurrence of acute symptoms after a period of partial or complete remission. Due to its variable aspects, there is no operational definition of relapse able to modelise the outcome of schizophrenia and measure how the treatment modifies the disease. Follow-up studies based on proxys such as hospital admission revealed that 7 of 10 patients relapsed after a first episode of schizophrenia. The effectiveness of antipsychotic medications on relapse prevention has been widely demonstrated. Recent studies claim for the advantages of atypical over first generation antipsychotic medication. Non-adherence to antipsychotic represents with addictions the main causes of relapse long before some non-consensual factors such as premorbid functioning, duration of untreated psychosis and associated personality disorders. The consequences of relapse are multiple, psychological, biological and social. Pharmaco-clinical studies have demonstrated that the treatment response decreases with each relapse. Relapse, even the first one, will contribute to worsen the outcome of the disease and reduce the capacity in general functionning. Accepting the idea of continuing treatment is a complex decision in which the psychiatrist plays a central role besides patients and their families. The development of integrated actions on modifiable risk factors such as psychosocial support, addictive comorbidities, access to care and the therapeutic alliance should be promoted. Relapse prevention is a major goal of the treatment of first-episode schizophrenia. It is based on adherence to the maintenance treatment, identification of prodromes, family active information and patient therapeutical education. Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

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

    Science.gov (United States)

    Rashidi, Armin; Cashen, Amanda F

    2015-01-01

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

  1. Potent anti-leukemia activities of humanized CD19-targeted CAR-T cells in patients with relapsed/refractory acute lymphoblastic leukemia.

    Science.gov (United States)

    Cao, Jiang; Wang, Gang; Cheng, Hai; Wei, Chen; Qi, Kunming; Sang, Wei; Zhenyu, Li; Shi, Ming; Li, Huizhong; Qiao, Jianlin; Pan, Bin; Zhao, Jing; Wu, Qingyun; Zeng, Lingyu; Niu, Mingshan; Jing, Guangjun; Zheng, Junnian; Xu, Kailin

    2018-04-10

    Chimeric antigen receptor T (CAR-T) cell therapy has shown promising results for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). The immune response induced by murine single-chain variable fragment (scFv) of the CAR may limit CAR-T cell persistence and thus increases the risk of leukemia relapse. In this study, we developed a novel humanized scFv from the murine FMC63 antibody. A total of 18 R/R ALL patients with or without prior murine CD19 CAR-T therapy were treated with humanized CD19-targeted CAR-T cells (hCART19s). After lymphodepletion chemotherapy with cyclophosphamide and fludarabine, the patients received a single dose (1 × 10 6 /kg) of autologous hCART19s infusion. Among the 14 patients without previous CAR-T therapy, 13 (92.9%) achieved complete remission (CR) or CR with incomplete count recovery (CRi) on day 30, whereas 1 of the 3 patients who failed a second murine CAR-T infusion achieved CR after hCART19s infusion. At day 180, the overall and leukemia-free survival rates were 65.8% and 71.4%, respectively. The cumulative incidence of relapse was 22.6%, and the non-relapse mortality rate was 7.1%. During treatment, 13 patients developed grade 1-2 cytokine release syndrome (CRS), 4 patients developed grade 3-5 CRS, and 1 patient experienced reversible neurotoxicity. These results indicated that hCART19s could induce remission in patients with R/R B-ALL, especially in patients who received a reinfusion of murine CAR-T. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  2. Ploidy and clinical characteristics of childhood acute myeloid leukemia

    DEFF Research Database (Denmark)

    Sandahl, Julie Damgaard; Kjeldsen, Eigil; Abrahamsson, Jonas

    2014-01-01

    We report the first large series (n = 596) of pediatric acute myeloid leukemia (AML) focusing on modal numbers (MN) from the population-based NOPHO-AML trials. Abnormal karyotypes were present in 452 cases (76%) and numerical aberrations were present in 40% (n = 237) of all pediatric AML. Among...... with early onset (median age 2 years), female sex (57%), and a dominance of acute megakaryoblastic leukemia (AMKL) (29%). Hypodiploidy constituted 8% of all AML and was associated with older age (median age 9 years), male predominance (60%), FAB M2 (56%), and t(8;21)(q22;q22) (56%) with loss of sex...

  3. Spontaneous Rapid Resolution of Acute Epidural Hematoma in Childhood

    Directory of Open Access Journals (Sweden)

    Ismail Gülşen

    2013-01-01

    Full Text Available Acute epidural hematoma is a critical emergency all around the world, and its aggressive diagnosis and treatment are of vital importance. Emergent surgical evacuation of the hematoma is known as standard management; however, conservative procedures are also used for small ones. Spontaneous rapid resolution of these hematomas has also been reported in eight pediatric cases. Various theories have been proposed to explain the underlying pathophysiology of this resolution. Herein, we are reporting a new pediatric case with spontaneously resolving acute epidural hematoma 12 hours after admission to the emergency room.

  4. Acute renal failure in infancy and childhood | Wiggelinkhuizen ...

    African Journals Online (AJOL)

    The clinical features and management of 132 infants and children with severe acute renal failure are reviewed. S. Afr. Med. J., 48, 2129 (1974). Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL.

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

    DEFF Research Database (Denmark)

    Borst, Louise; Buchard, Anders; Rosthoj, Susanne

    2012-01-01

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

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

    DEFF Research Database (Denmark)

    Borst, Louise; Wesolowska, Agata; Joshi, Tejal

    2012-01-01

    The chromosomal translocation t(12;21) resulting in the ETV6/RUNX1 fusion gene is the most frequent structural cytogenetic abnormality among patients with childhood acute lymphoblastic leukaemia (ALL). We investigated 62 ETV6/RUNX1‐positive childhood ALL patients by single nucleotide polymorphism...... childhood ALL, which may be important for understanding poor responses among this otherwise highly curable subset of ALL and lead to novel targeted treatment strategies....

  7. A prospective neurocognitive evaluation of children treated with additional chemotherapy and craniospinal irradiation following isolated central nervous system relapse in acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Kumar, Parvesh; Mulhern, Raymond K.; Regine, William F.; Rivera, Gaston K.; Kun, Larry E.

    1995-01-01

    Purpose: A prospective assessment of neurocognitive performance was conducted in children with acute lymphoblastic leukemia (ALL) following isolated central nervous system (CNS) relapse to evaluate the impact of additional systemic/intrathecal (IT) chemotherapy and craniospinal irradiation (CSI) upon long-term intellectual function. Methods and Materials: Twenty-one children with ALL manifesting an isolated CNS relapse between 1984 through 1989 underwent serial evaluations of intellectual function. Neurocognitive function was measured by the full-scale intelligence quotient (FSIQ) as determined by the age-appropriate Wechsler Intelligence Scale and by achievement in reading, math, and spelling as assessed by the Wide Range Achievement Test (WRAT). Intelligence testing was initiated following isolated CNS relapse after clearance of cerebrospinal fluid (CSF) cytology but prior to CSI and continued at annual intervals for a minimum of 4 years postmeningeal failure. Protocol treatment for isolated CNS relapse consisted of reinduction and maintenance systemic therapy, intrathecal (IT) triple-agent chemotherapy, and early CSI (cranium to 24 Gy and spine to 15 Gy at 1.5 Gy/fraction) as outlined on the institutional 'Total XI' trial. Results: All 21 children attained secondary CNS remission and underwent the planned additional systemic/IT chemotherapy and CSI. Fourteen of the 21 children remain in secondary continuous remission, while the remaining 7 experienced a second relapse and were removed from further neurocognitive assessment. For the eight female and six male long-term survivors, mean ages at original diagnosis and at CSI were 5.7 years (range = 0.6-16.2) and 7.0 years (range = 1.8-17.0), respectively. At a median follow-up interval of 4.6 years (ranges 1.7-6.8) post-CNS relapse, comparison of group mean initial to final FSIQs revealed no statistically significant difference between the two measures (94.5 vs. 95.9, respectively, n = 11, p = 0.52). None of the

  8. Simple diagnosis of benign acute childhood myositis: Lessons from a case report.

    Science.gov (United States)

    Terlizzi, Vito; Improta, Federica; Raia, Valeria

    2014-01-01

    Acute muscle pain and walking difficulty are symptoms compatible with both benign and severe degenerative diseases. As a consequence, in some cases invasive tests and hospitalizations are improperly scheduled. We report the case of a 7-year-old child suffering from acute calf pain and abnormal gait following flu-like symptoms. A review of the literature will be helpful to better define differential diagnosis in cases of muscle pain in children. Daily physical examination and urine dipstick are sufficient to confirm the diagnosis of benign acute childhood myositis (BACM) during the acute phase, to promptly detect severe complications and to rule out degenerative diseases. Children with BACM do not require hospitalization, medical interventions or long-term follow-up.

  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. Cost-analysis of treatment of childhood acute lymphoblastic leukemia with asparaginase preparations: The impact of expensive chemotherapy

    NARCIS (Netherlands)

    W.H. Tong (Wing); I.M. van der Sluis (Inge); C.J.M. Alleman (Cathelijne); R.R. van Litsenburg (Raphaële ); G.J. Kaspers (Gertjan); R. Pieters (Rob); C.A. Uyl-de Groot (Carin)

    2013-01-01

    markdownabstract__Abstract__ Asparaginase is an expensive drug, but important in childhood acute lymphoblastic leukemia. In order to compare costs of PEGasparaginase, Erwinia asparaginase and native E. coli asparaginase, we performed a cost-analysis in the Dutch Childhood Oncology Group ALL-10

  11. 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 but ...

  12. Chemotherapy versus Hypomethylating Agents for the Treatment of Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome after Allogeneic Stem Cell Transplant.

    Science.gov (United States)

    Motabi, Ibraheem H; Ghobadi, Armin; Liu, Jingxia; Schroeder, Mark; Abboud, Camille N; Cashen, Amanda F; Stockler-Goldstein, Keith E; Uy, Geoffrey L; Vij, Ravi; Westervelt, Peter; DiPersio, John F

    2016-07-01

    Allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). For patients with relapsed disease after transplantation, intensive chemotherapy followed by donor lymphocyte infusion (DLI) or a second allo-SCT may result in a durable response in some patients. High-intensity chemotherapy and less aggressive therapy with hypomethylating agents (HAs) with and without DLI are often used for relapse after allo-SCT. Here we compared the treatment outcomes of intensive chemotherapy with that of HAs in relapsed AML and MDS after allo-SCT. Patients who had received a second SCT within 90 days of the relapse date were excluded. The primary endpoints were overall response rate (ORR) and overall survival (OS). Secondary endpoints were complete remission (CR) rate and progression-free survival (PFS). One hundred patients were included: 73 patients received chemotherapy and 27 patients received an HA. Fifty-six percent of patients in the chemotherapy group and 33% of patients in the HA group received at least 1 DLI after treatment. Treatment with chemotherapy resulted in a higher ORR (51% versus 19%, P = .004) and a higher CR rate (40% versus 7%, P = .002). The median OS (6 versus 3.9 months, P = .01) and PFS (4.9 versus 3.8 months, P = .02) were longer in the chemotherapy group. Similar benefit of chemotherapy over HAs was maintained in all treatment outcomes after controlling for the use of DLI. The use of chemotherapy followed by DLI offered the greatest benefit (ORR, 68%; CR, 59%, 1-year OS, 44%; and median OS, 9.8 months). In conclusion, in our hands, with limited numbers, the use of more conventional salvage chemotherapy, with DLI when possible, for the treatment of relapsed AML and MDS after allo-SCT is associated with better outcomes than nonchemotherapy (HA) options. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier

  13. 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...... leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CONCLUSION: CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia....

  14. Acute necrotising encephalopathy of childhood after exanthema subitum outside Japan or Taiwan

    Energy Technology Data Exchange (ETDEWEB)

    Porto, L.; Lanferman, H.; Moeller-Hartmann, W.; Jacobi, G.; Zanella, F. [Inst. fuer Neuroradiologie, Klinikum der Johann Wolfgang Goethe-Univ., Frankfurt am Main (Germany)

    1999-10-01

    Acute necrotising encephalopathy of childhood (ANE) is an uncommon disease which predominantly affects infants and young children living in Japan and Taiwan. A multifocal encephalopathy with symmetrical lesions in the thalamus, tegmentum of the brain stem, cerebral periventricular white matter and cerebellar medulla is characteristic. We present the imaging features in a 4-year-old Japanese boy who had been living in Germany for 2{sup 1}/{sub 2} years before presentation. (orig.)

  15. Acute necrotising encephalopathy of childhood after exanthema subitum outside Japan or Taiwan

    International Nuclear Information System (INIS)

    Porto, L.; Lanferman, H.; Moeller-Hartmann, W.; Jacobi, G.; Zanella, F.

    1999-01-01

    Acute necrotising encephalopathy of childhood (ANE) is an uncommon disease which predominantly affects infants and young children living in Japan and Taiwan. A multifocal encephalopathy with symmetrical lesions in the thalamus, tegmentum of the brain stem, cerebral periventricular white matter and cerebellar medulla is characteristic. We present the imaging features in a 4-year-old Japanese boy who had been living in Germany for 2 1 / 2 years before presentation. (orig.)

  16. Virus detection and cytokine profile in relation to age among acute exacerbations of childhood asthma.

    Science.gov (United States)

    Kato, Masahiko; Suzuki, Kazuo; Yamada, Yoshiyuki; Maruyama, Kenichi; Hayashi, Yasuhide; Mochizuki, Hiroyuki

    2015-09-01

    Little information is available regarding eosinophil activation and cytokine profiles in relation to age in virus-induced bronchial asthma. We therefore explored the association between age, respiratory viruses, serum eosinophil cationic protein (ECP), and cytokines/chemokines in acute exacerbations of childhood asthma. We investigated viruses in nasal secretions from 88 patients with acute exacerbation of childhood asthma by using antigen detection kits and/or RT-PCR, followed by direct DNA sequencing analysis. We also measured peripheral eosinophil counts, and the serum levels of ECP and 27 types of cytokines/chemokines in 71 virus-induced acute asthma cases and 13 controls. Viruses were detected in 71(80.7%) of the 88 samples. The three major viruses detected were rhinoviruses, RS viruses, and enteroviruses; enteroviruses were found to be dominant in patients aged ≥3 years. There was no change in the levels of rhinoviruses and RS viruses between the two age groups, defined as children aged asthma cases compared with controls. Serum ECP values were significantly higher in patients with virus-induced asthma at age ≥3 years compared with those aged asthma in patients childhood asthma. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

    Schrappe, M.

    2008-01-01

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

  18. Maintenance therapy of childhood acute lymphoblastic leukemia revisited-Should drug doses be adjusted by white blood cell, neutrophil, or lymphocyte counts?

    Science.gov (United States)

    Schmiegelow, Kjeld; Nersting, Jacob; Nielsen, Stine Nygaard; Heyman, Mats; Wesenberg, Finn; Kristinsson, Jon; Vettenranta, Kim; Schrøeder, Henrik; Weinshilboum, Richard; Jensen, Katrine Lykke; Grell, Kathrine; Rosthoej, Susanne

    2016-12-01

    6-Mercaptopurine (6MP) and methotrexate (MTX) based maintenance therapy is a critical phase of childhood acute lymphoblastic leukemia treatment. Wide interindividual variations in drug disposition warrant frequent doses adjustments, but there is a lack of international consensus on dose adjustment guidelines. To identify relapse predictors, we collected 28,255 data sets on drug doses and blood counts (median: 47/patient) and analyzed erythrocyte (Ery) levels of cytotoxic 6MP/MTX metabolites in 9,182 blood samples (median: 14 samples/patient) from 532 children on MTX/6MP maintenance therapy targeted to a white blood cell count (WBC) of 1.5-3.5 × 10 9 /l. After a median follow-up of 13.8 years for patients in remission, stepwise Cox regression analysis did not find age, average doses of 6MP and MTX, hemoglobin, absolute lymphocyte counts, thrombocyte counts, or Ery levels of 6-thioguanine nucleotides or MTX (including its polyglutamates) to be significant relapse predictors. The parameters significantly associated with risk of relapse (N = 83) were male sex (hazard ratio [HR] 2.0 [1.3-3.1], P = 0.003), WBC at diagnosis (HR = 1.04 per 10 × 10 9 /l rise [1.00-1.09], P = 0.048), the absolute neutrophil count (ANC; HR = 1.7 per 10 9 /l rise [1.3-2.4], P = 0.0007), and Ery thiopurine methyltransferase activity (HR = 2.7 per IU/ml rise [1.1-6.7], P = 0.03). WBC was significantly related to ANC (Spearman correlation coefficient, r s  = 0.77; P best hematological target for dose adjustments of maintenance therapy. © 2016 Wiley Periodicals, Inc.

  19. Cranial radiation in childhood acute lymphocytic leukemia. Neuropsychologic sequelae

    International Nuclear Information System (INIS)

    Whitt, J.K.; Wells, R.J.; Lauria, M.M.; Wilhelm, C.L.; McMillan, C.W.

    1984-01-01

    A battery of neuropsychologic tests was administered ''blindly'' to 18 children with acute lymphocytic leukemia (ALL) who had been randomly assigned to treatment regimens with or without cranial radiation. These children were all in complete continuous remission for more than 3 1/2 years and were no longer receiving therapy. The results indicated no substantial differences between groups as a function of radiation therapy. However, decreased neuropsychologic performance was found when the entire sample was compared with population norms. These data do not support the hypothesis that cranial radiation therapy is responsible for the neuropsychologic sequelae seen in these survivors of ALL. Post hoc multiple regression analysis indicated that parental education levels accounted for more of the neuropsychologic variability seen in these children than other factors such as age at diagnosis, type of therapy, or sex of child

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

    NARCIS (Netherlands)

    A. Holleman (Amy); M.L. den Boer (Monique); K.M. Kazemier (Karin); H.B. Beverloo (Berna); A.R.M. von Bergh (Anne); G.E. Janka-Schaub (Gritta); R. Pieters (Rob)

    2005-01-01

    textabstractDrug resistance in childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) is associated with impaired ability to induce apoptosis. To elucidate causes of apoptotic defects, we studied the protein expression of Apaf-1, procaspases-2, -3, -6, -7,

  1. Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study.

    Science.gov (United States)

    Ravandi, Farhad; Ritchie, Ellen K; Sayar, Hamid; Lancet, Jeffrey E; Craig, Michael D; Vey, Norbert; Strickland, Stephen A; Schiller, Gary J; Jabbour, Elias; Erba, Harry P; Pigneux, Arnaud; Horst, Heinz-August; Recher, Christian; Klimek, Virginia M; Cortes, Jorge; Roboz, Gail J; Odenike, Olatoyosi; Thomas, Xavier; Havelange, Violaine; Maertens, Johan; Derigs, Hans-Günter; Heuser, Michael; Damon, Lloyd; Powell, Bayard L; Gaidano, Gianluca; Carella, Angelo-Michele; Wei, Andrew; Hogge, Donna; Craig, Adam R; Fox, Judith A; Ward, Renee; Smith, Jennifer A; Acton, Gary; Mehta, Cyrus; Stuart, Robert K; Kantarjian, Hagop M

    2015-09-01

    Safe and effective treatments are urgently needed for patients with relapsed or refractory acute myeloid leukaemia. We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed or refractory acute myeloid leukaemia. This phase 3, double-blind, placebo-controlled trial was undertaken at 101 international sites. Eligible patients with acute myeloid leukaemia were aged 18 years of age or older and had refractory disease or were in first relapse after one or two cycles of previous induction chemotherapy, including at least one cycle of anthracycline (or anthracenedione) plus cytarabine. Patients were randomly assigned 1:1 to vosaroxin (90 mg/m(2) intravenously on days 1 and 4 in a first cycle; 70 mg/m(2) in subsequent cycles) plus cytarabine (1 g/m(2) intravenously on days 1-5) or placebo plus cytarabine through a central interactive voice system with a permuted block procedure stratified by disease status, age, and geographical location. All participants were masked to treatment assignment. The primary efficacy endpoint was overall survival and the primary safety endpoint was 30-day and 60-day all-cause mortality. Efficacy analyses were done by intention to treat; safety analyses included all treated patients. This study is registered with ClinicalTrials.gov, number NCT01191801. Between Dec 17, 2010, and Sept 25, 2013, 711 patients were randomly assigned to vosaroxin plus cytarabine (n=356) or placebo plus cytarabine (n=355). At the final analysis, median overall survival was 7·5 months (95% CI 6·4-8·5) in the vosaroxin plus cytarabine group and 6·1 months (5·2-7·1) in the placebo plus cytarabine group (hazard ratio 0·87, 95% CI 0·73-1·02; unstratified log-rank p=0·061; stratified p=0·024). A higher proportion of patients achieved complete remission in the vosaroxin plus cytarabine group than in the placebo plus cytarabine group (107 [30%] of 356 patients vs 58 [16%] of 355

  2. Integration of childhood TB into guidelines for the management of acute malnutrition in high burden countries.

    Science.gov (United States)

    Patel, L N; Detjen, A K

    2017-06-21

    Introduction: Childhood tuberculosis (TB) and undernutrition are major global public health challenges. In 2015, although an estimated 1 million children aged malnutrition from 17 high TB burden countries were reviewed to gather information on TB symptom screening, exposure history, and treatment. Results: Seven (41%) countries recommend routine TB screening among children with acute malnutrition, and six (35%) recommend obtaining a TB exposure history. Conclusion: TB screening is not consistently included in guidelines for acute malnutrition in high TB burden countries. Routine TB risk assessment, especially history of TB exposure, among acutely malnourished children, combined with improved linkages with TB services, would help increase TB case finding and could impact outcomes. Operational research on how best to integrate services at different levels of the health care system is needed.

  3. The clinical significance of lung hypoexpansion in acute childhood asthma

    International Nuclear Information System (INIS)

    Spottswood, Stephanie E.; Allison, Kelley Z.; Narla, Lakshmana D.; Lowry, Patricia A.; Lopatina, Olga A.; Sethi, Narinder N.; Nettleman, Mary D.

    2004-01-01

    Many children experiencing acute asthmatic episodes have chest radiographs, which may show lung hyperinflation, hypoinflation, or normal inflation. Lung hypoinflation may be a sign of respiratory fatigue and poor prognosis. To compare the clinical course in children with asthma according to the degree of lung inflation on chest radiographs. We conducted a retrospective study during a 24-month period (from July 1999 to July 2001) of children aged 0-17 years, who presented to a pediatric emergency department or outpatient clinic with an asthma exacerbation. Chest radiographs obtained at presentation were reviewed independently by three pediatric radiologists who were blinded to the admission status of the patient. The correlation between hypoinflation and hospital admission was assessed in three age groups: 0-2 years, 3-5 years, and 6-17 years. Hypoinflation on chest radiographs was significantly correlated with hospital admission for children aged 6-17 years (odds ratio 16.00, 95% confidence interval 1.89-135.43). The inter-reader agreement for interpretation of these radiographs was strong, with a kappa score of 0.76. Hypoinflation was not correlated with admission in younger children. Lung hypoinflation is associated with a greater likelihood of hospital admission in children aged 6 years or older. Therefore, hypoinflation was a poor prognostic sign and may warrant more aggressive therapy. (orig.)

  4. The clinical significance of lung hypoexpansion in acute childhood asthma

    Energy Technology Data Exchange (ETDEWEB)

    Spottswood, Stephanie E. [Department of Radiology, Medical College of Virginia, Virginia Commonwealth University Health System, Box 980615, 23298-0615, Richmond, VA (United States); Department of Radiology, The Children' s Hospital of the King' s Daughters, 601 Children' s Lane, Norfolk, VA 23507 (United States); Allison, Kelley Z.; Narla, Lakshmana D.; Lowry, Patricia A. [Department of Radiology, Medical College of Virginia, Virginia Commonwealth University Health System, Box 980615, 23298-0615, Richmond, VA (United States); Lopatina, Olga A.; Sethi, Narinder N. [School of Medicine, Medical College of Virginia, Virginia Commonwealth University Health System, Richmond, VA (United States); Nettleman, Mary D. [Department of Internal Medicine, B-427 Clinical Center, Michigan State University, East Lansing, MI 48824 (United States)

    2004-04-01

    Many children experiencing acute asthmatic episodes have chest radiographs, which may show lung hyperinflation, hypoinflation, or normal inflation. Lung hypoinflation may be a sign of respiratory fatigue and poor prognosis. To compare the clinical course in children with asthma according to the degree of lung inflation on chest radiographs. We conducted a retrospective study during a 24-month period (from July 1999 to July 2001) of children aged 0-17 years, who presented to a pediatric emergency department or outpatient clinic with an asthma exacerbation. Chest radiographs obtained at presentation were reviewed independently by three pediatric radiologists who were blinded to the admission status of the patient. The correlation between hypoinflation and hospital admission was assessed in three age groups: 0-2 years, 3-5 years, and 6-17 years. Hypoinflation on chest radiographs was significantly correlated with hospital admission for children aged 6-17 years (odds ratio 16.00, 95% confidence interval 1.89-135.43). The inter-reader agreement for interpretation of these radiographs was strong, with a kappa score of 0.76. Hypoinflation was not correlated with admission in younger children. Lung hypoinflation is associated with a greater likelihood of hospital admission in children aged 6 years or older. Therefore, hypoinflation was a poor prognostic sign and may warrant more aggressive therapy. (orig.)

  5. Philadelphia chromosome-positive acute lymphoblastic leukemia in childhood

    Directory of Open Access Journals (Sweden)

    Hong Hoe Koo

    2011-03-01

    Full Text Available In pediatric patients with acute lymphoblastic leukemia (ALL, the Philadelphia chromosome translocation is uncommon, with a frequency of less than 5%. However, it is classified as a high or very high risk, and only 20&#8210;30% of Philadelphia chromosome-positive (Ph+ children with ALL are cured with chemotherapy alone. Allogeneic hematopoietic stem cell transplantation from a closely matched donor cures 60% of patients in first complete remission. Recent data suggest that chemotherapy plus tyrosine kinase inhibitors (TKIs may be the initial treatment of choice for Ph+ ALL in children. However, longer observation is required to determine whether long-term outcome with intensive imatinib and chemotherapy is indeed equivalent to that with allogeneic related or alternative donor hematopoietic stem cell transplantation (HSCT. Reports on the use of second-generation TKIs in children with Ph+ ALL are limited. A few case reports have indicated the feasibility and clinical benefit of using dasatinib as salvage therapy enabling HSCT. However, more extensive data from clinical trials are needed to determine whether the administration of secondgeneration TKIs in children is comparable to that in adults. Because Ph+ ALL is rare in children, the question of whether HSCT could be a dispensable part of their therapy may not be answered for some time. An international multicenter study is needed to answer the question of whether imatinib plus chemotherapy could replace sibling allogeneic HSCT in children with Ph+ ALL.

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

    Directory of Open Access Journals (Sweden)

    F. Azevedo-Silva

    2010-03-01

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

  7. Constitutional sequence variation in the Fanconi anaemia group C (FANCC) gene in childhood acute myeloid leukaemia.

    Science.gov (United States)

    Barber, Lisa M; McGrath, Helen E N; Meyer, Stefan; Will, Andrew M; Birch, Jillian M; Eden, Osborn B; Taylor, G Malcolm

    2003-04-01

    The extent to which genetic susceptibility contributes to the causation of childhood acute myeloid leukaemia (AML) is not known. The inherited bone marrow failure disorder Fanconi anaemia (FA) carries a substantially increased risk of AML, raising the possibility that constitutional variation in the FA (FANC) genes is involved in the aetiology of childhood AML. We have screened genomic DNA extracted from remission blood samples of 97 children with sporadic AML and 91 children with sporadic acute lymphoblastic leukaemia (ALL), together with 104 cord blood DNA samples from newborn children, for variations in the Fanconi anaemia group C (FANCC) gene. We found no evidence of known FANCC pathogenic mutations in children with AML, ALL or in the cord blood samples. However, we detected 12 different FANCC sequence variants, of which five were novel to this study. Among six FANCC variants leading to amino-acid substitutions, one (S26F) was present at a fourfold greater frequency in children with AML than in the cord blood samples (odds ratio: 4.09, P = 0.047; 95% confidence interval 1.08-15.54). Our results thus do not exclude the possibility that this polymorphic variant contributes to the risk of a small proportion of childhood AML.

  8. Severe Hypertriglyceridemia During Therapy For Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Bhojwani, Deepa; Darbandi, Rashid; Pei, Deqing; Ramsey, Laura B.; Chemaitilly, Wassim; Sandlund, John T.; Cheng, Cheng; Pui, Ching-Hon; Relling, Mary V.; Jeha, Sima; Metzger, Monika L.

    2014-01-01

    Background Asparaginase and steroids can cause hypertriglyceridemia in children with acute lymphoblastic leukemia (ALL). There are no guidelines for screening or management of patients with severe hypertriglyceridemia (>1000 mg/dL) during ALL therapy. Patients and Methods Fasting lipid profiles were obtained prospectively at 4 time-points for 257 children consecutively enrolled on a frontline ALL study. Risk factors were evaluated by the exact chi-square test. Details of adverse events and management of hypertriglyceridemia were extracted retrospectively. Results Eighteen of 257 (7%) patients developed severe hypertriglyceridemia. Older age and treatment with higher doses of asparaginase and steroids on the standard/high-risk arm were significant risk factors. Severe hypertriglyceridemia was not associated with pancreatitis after adjustment for age and treatment arm or with osteonecrosis after adjustment for age. However, patients with severe hypertriglyceridemia had a 2.5 to 3 times higher risk of thrombosis compared to patients without, albeit the difference was not statistical significant. Of the 30 episodes of severe hypertriglyceridemia in 18 patients, 7 were managed conservatively while the others with pharmacotherapy. Seventeen of 18 patients continued to receive asparaginase and steroids. Triglyceride levels normalized after completion of ALL therapy in all 12 patients with available measurements. Conclusion Asparaginase- and steroid-induced transient hypertriglyceridemia can be adequately managed with dietary modifications and close monitoring without altering chemotherapy. Patients with severe hypertriglyceridemia were not at increased risk of adverse events, with a possible exception of thrombosis. The benefit of pharmacotherapy in decreasing symptoms and potential complications requires further investigation. PMID:25087182

  9. 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

    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...

  10. Visual Attention and Math Performance in Survivors of Childhood Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Richard, Annette E; Hodges, Elise K; Heinrich, Kimberley P

    2018-01-24

    Attentional and academic difficulties, particularly in math, are common in survivors of childhood acute lymphoblastic leukemia (ALL). Of cognitive deficits experienced by survivors of childhood ALL, attention deficits may be particularly responsive to intervention. However, it is unknown whether deficits in particular aspects of attention are associated with deficits in math skills. The current study investigated relationships between math calculation skills, performance on an objective measure of sustained attention, and parent- and teacher-reported attention difficulties. Twenty-four survivors of childhood ALL (Mage = 13.5 years, SD= 2.8 years) completed a computerized measure of sustained attention and response control and a written measure of math calculation skills in the context of a comprehensive clinical neuropsychological evaluation. Parent and teacher ratings of inattention and impulsivity were obtained. Visual response control and visual attention accounted for 26.4% of the variance observed among math performance scores after controlling for IQ (p < .05). Teacher-rated, but not parent-rated, inattention was significantly negatively correlated with math calculation scores. Consistency of responses to visual stimuli on a computerized measure of attention is a unique predictor of variance in math performance among survivors of childhood ALL. Objective testing of visual response control, rather than parent-rated attentional problems, may have clinical utility in identifying ALL survivors at risk for math difficulties. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Mercaptopurine Ingestion Habits, Red Cell Thioguanine Nucleotide Levels, and Relapse Risk in Children With Acute Lymphoblastic Leukemia: A Report From the Children’s Oncology Group Study AALL03N1

    Science.gov (United States)

    Landier, Wendy; Hageman, Lindsey; Chen, Yanjun; Kornegay, Nancy; Evans, William E.; Bostrom, Bruce C.; Casillas, Jacqueline; Dickens, David S.; Angiolillo, Anne L.; Lew, Glen; Maloney, Kelly W.; Mascarenhas, Leo; Ritchey, A. Kim; Termuhlen, Amanda M.; Carroll, William L.; Relling, Mary V.; Wong, F. Lennie

    2017-01-01

    Purpose Children with acute lymphoblastic leukemia (ALL) are generally instructed to take mercaptopurine (6-MP) in the evening and without food or dairy products. This study examines the association between 6-MP ingestion habits and 6-MP adherence, red cell thioguanine nucleotide (TGN) levels, and risk of relapse in children with TMPT wild-type genotype. Methods Participants included 441 children with ALL receiving oral 6-MP for maintenance. Adherence was monitored over 48,086 patient-days using the Medication Event Monitoring System; nonadherence was defined as adherence rate < 95%. 6-MP ingestion habits examined included: takes 6-MP with versus never with food, takes 6-MP with versus never with dairy, and takes 6-MP in the evening versus morning versus varying times. Results Median age at study was 6 years (range, 2 to 20 years); 43.8% were nonadherent. Certain 6-MP ingestion habits were associated with nonadherence (taking 6-MP with dairy [odds ratio (OR), 1.9; 95% CI, 1.3 to 2.9; P = .003] and at varying times [OR, 3.4; 95% CI, 1.8 to 6.3; P = .0001]). After adjusting for adherence and other prognosticators, there was no association between 6-MP ingestion habits and relapse risk (6-MP with food: hazard ratio [HR], 0.7; 95% CI, 0.3 to 1.9; P = .5; with dairy: HR, 0.3; 95% CI, 0.07 to 1.5; P = .2; taken in evening/night: HR, 1.1; 95% CI, 0.2 to 7.8; P = .9; at varying times: HR, 0.3; 95% CI, 0.04 to 2.7; P = .3). Among adherent patients, there was no association between red cell TGN levels and taking 6-MP with food versus without (206.1 ± 107.1 v 220.6 ± 121.6; P = .5), with dairy versus without (220.1 ± 87.8 v 216.3 ± 121.3; P =.7), or in the evening/night versus morning/midday versus varying times (218.8 ± 119.7 v 195.5 ± 82.3 v 174.8 ± 93.4; P = .6). Conclusion Commonly practiced restrictions surrounding 6-MP ingestion might not influence outcome but may hinder adherence. Future recommendations regarding 6-MP intake during maintenance therapy for

  12. Mercaptopurine Ingestion Habits, Red Cell Thioguanine Nucleotide Levels, and Relapse Risk in Children With Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group Study AALL03N1.

    Science.gov (United States)

    Landier, Wendy; Hageman, Lindsey; Chen, Yanjun; Kornegay, Nancy; Evans, William E; Bostrom, Bruce C; Casillas, Jacqueline; Dickens, David S; Angiolillo, Anne L; Lew, Glen; Maloney, Kelly W; Mascarenhas, Leo; Ritchey, A Kim; Termuhlen, Amanda M; Carroll, William L; Relling, Mary V; Wong, F Lennie; Bhatia, Smita

    2017-05-20

    Purpose Children with acute lymphoblastic leukemia (ALL) are generally instructed to take mercaptopurine (6-MP) in the evening and without food or dairy products. This study examines the association between 6-MP ingestion habits and 6-MP adherence, red cell thioguanine nucleotide (TGN) levels, and risk of relapse in children with TMPT wild-type genotype. Methods Participants included 441 children with ALL receiving oral 6-MP for maintenance. Adherence was monitored over 48,086 patient-days using the Medication Event Monitoring System; nonadherence was defined as adherence rate < 95%. 6-MP ingestion habits examined included: takes 6-MP with versus never with food, takes 6-MP with versus never with dairy, and takes 6-MP in the evening versus morning versus varying times. Results Median age at study was 6 years (range, 2 to 20 years); 43.8% were nonadherent. Certain 6-MP ingestion habits were associated with nonadherence (taking 6-MP with dairy [odds ratio (OR), 1.9; 95% CI, 1.3 to 2.9; P = .003] and at varying times [OR, 3.4; 95% CI, 1.8 to 6.3; P = .0001]). After adjusting for adherence and other prognosticators, there was no association between 6-MP ingestion habits and relapse risk (6-MP with food: hazard ratio [HR], 0.7; 95% CI, 0.3 to 1.9; P = .5; with dairy: HR, 0.3; 95% CI, 0.07 to 1.5; P = .2; taken in evening/night: HR, 1.1; 95% CI, 0.2 to 7.8; P = .9; at varying times: HR, 0.3; 95% CI, 0.04 to 2.7; P = .3). Among adherent patients, there was no association between red cell TGN levels and taking 6-MP with food versus without (206.1 ± 107.1 v 220.6 ± 121.6; P = .5), with dairy versus without (220.1 ± 87.8 v 216.3 ± 121.3; P =.7), or in the evening/night versus morning/midday versus varying times (218.8 ± 119.7 v 195.5 ± 82.3 v 174.8 ± 93.4; P = .6). Conclusion Commonly practiced restrictions surrounding 6-MP ingestion might not influence outcome but may hinder adherence. Future recommendations regarding 6-MP intake during maintenance therapy for

  13. [Evaluation of association between an acute attack of childhood bronchial asthma and Chlamydia pneumoniae infection].

    Science.gov (United States)

    Jiang, Yi; Liu, Xing-Lian; Xing, Fu-Qiang; Yang, Ju-Sheng; Tu, Hong

    2006-04-01

    To identify whether there is an association between an acute attack of childhood bronchial asthma and Chlamydia pneumoniae (CP) infection. Serum specific antibodies IgM and IgG to CP were detected by ELISA in 120 asthmatic children with an acute attack and 82 healthy children. Anti-CP IgM was demonstrated in 22 cases (18.3%) and anti-CP IgG was demonstrated in 32 cases (26.7%) out of the 120 asthmatic patients. The incidence of CP infection in asthmatic children was significantly higher than that in healthy controls (3.7%) (P attack of asthma in 15 cases out of the 32 cases with CP infection, but 17 cases required glucocorticoid inhalation treatment together with anti-CP infection treatment (macrolide antibiotics, eg. azithromycin) for remission of asthma attack. There may be a link between an acute attack of childhood asthma and CP infection. It is thus necessary to detect the CP-specific antibodies in asthmatic children for proper treatment.

  14. Childhood central nervous system leukemia: historical perspectives, current therapy, and acute neurological sequelae

    Energy Technology Data Exchange (ETDEWEB)

    Laningham, Fred H. [St. Jude Children' s Research Hospital, Division of Diagnostic Imaging, Department of Radiological Sciences, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States); Kun, Larry E. [St. Jude Children' s Research Hospital, Division of Radiation Oncology, Department of Radiological Sciences, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States); Reddick, Wilburn E.; Ogg, Robert J. [St. Jude Children' s Research Hospital, Division of Translational Imaging Research, Department of Radiological Sciences, Memphis, TN (United States); Morris, E.B. [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); Pui, Ching-Hon [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States)

    2007-11-15

    During the past three decades, improvements in the treatment of childhood leukemia have resulted in high cure rates, particularly for acute lymphoblastic leukemia (ALL). Unfortunately, successful therapy has come with a price, as significant morbidity can result from neurological affects which harm the brain and spinal cord. The expectation and hope is that chemotherapy, as a primary means of CNS therapy, will result in acceptable disease control with less CNS morbidity than has been observed with combinations of chemotherapy and radiotherapy over the past several decades. In this review we discuss the poignant, historical aspects of CNS leukemia therapy, outline current methods of systemic and CNS leukemia therapy, and present imaging findings we have encountered in childhood leukemia patients with a variety of acute neurological conditions. A major objective of our research is to understand the neuroimaging correlates of acute and chronic effects of cancer and therapy. Specific features related to CNS leukemia and associated short-term toxicities, both disease- and therapy-related, are emphasized in this review with the specific neuroimaging findings. Specific CNS findings are similarly important when treating acute myelogenous leukemia (AML), and details of leukemic involvement and toxicities are also presented in this entity. Despite contemporary treatment approaches which favor the use of chemotherapy (including intrathecal therapy) over radiotherapy in the treatment of CNS leukemia, children still occasionally experience morbid neurotoxicity. Standard neuroimaging is sufficient to identify a variety of neurotoxic sequelae in children, and often suggest specific etiologies. Specific neuroimaging findings frequently indicate a need to alter antileukemia therapy. It is important to appreciate that intrathecal and high doses of systemic chemotherapy are not innocuous and are associated with acute, specific, recognizable, and often serious neurological

  15. Childhood central nervous system leukemia: historical perspectives, current therapy, and acute neurological sequelae

    International Nuclear Information System (INIS)

    Laningham, Fred H.; Kun, Larry E.; Reddick, Wilburn E.; Ogg, Robert J.; Morris, E.B.; Pui, Ching-Hon

    2007-01-01

    During the past three decades, improvements in the treatment of childhood leukemia have resulted in high cure rates, particularly for acute lymphoblastic leukemia (ALL). Unfortunately, successful therapy has come with a price, as significant morbidity can result from neurological affects which harm the brain and spinal cord. The expectation and hope is that chemotherapy, as a primary means of CNS therapy, will result in acceptable disease control with less CNS morbidity than has been observed with combinations of chemotherapy and radiotherapy over the past several decades. In this review we discuss the poignant, historical aspects of CNS leukemia therapy, outline current methods of systemic and CNS leukemia therapy, and present imaging findings we have encountered in childhood leukemia patients with a variety of acute neurological conditions. A major objective of our research is to understand the neuroimaging correlates of acute and chronic effects of cancer and therapy. Specific features related to CNS leukemia and associated short-term toxicities, both disease- and therapy-related, are emphasized in this review with the specific neuroimaging findings. Specific CNS findings are similarly important when treating acute myelogenous leukemia (AML), and details of leukemic involvement and toxicities are also presented in this entity. Despite contemporary treatment approaches which favor the use of chemotherapy (including intrathecal therapy) over radiotherapy in the treatment of CNS leukemia, children still occasionally experience morbid neurotoxicity. Standard neuroimaging is sufficient to identify a variety of neurotoxic sequelae in children, and often suggest specific etiologies. Specific neuroimaging findings frequently indicate a need to alter antileukemia therapy. It is important to appreciate that intrathecal and high doses of systemic chemotherapy are not innocuous and are associated with acute, specific, recognizable, and often serious neurological

  16. Improved outcome of childhood acute myeloid leukemia in an Eastern European country: Lithuanian experience.

    Science.gov (United States)

    Kairiene, Igne; Pasauliene, Ramune; Lipunova, Nadezda; Vaitkeviciene, Goda; Rageliene, Lina; Rascon, Jelena

    2017-10-01

    The reported treatment outcomes of children treated for cancer in Eastern European countries are inferior to those in Northern/Western Europe. We hypothesized that recent survival rates could be comparable to the current standards and performed a population-based analysis of treatment outcome of childhood acute myeloid leukemia (AML) in Lithuania, a small Eastern European country. Children  80% in high-income countries. The difference in survival rates between Northern/Western and Eastern European countries as well as between high- and middle-/low-income countries is as much as 20%. Recently, the 5-year event-free survival rate of acute myeloid leukemia (AML) has reached > 60% in high-income countries. The survival rates for myeloproliferative diseases were the lowest in Eastern European countries. • The reported inferior survival rates were calculated based on outcome data of patients treated until 2007. The recent survival rates in Eastern European countries are unknown. What is New: • Being a small Eastern European country, Lithuania has experienced good economic growth during the last decade. We hypothesized that economic growth and gain of experience could result in better survival rates of children treated for cancer in our country in recent years. • A population-based analysis of treatment outcome of childhood AML treated in Lithuania in the recent years was performed for the first time. The survival rates of childhood AML in Lithuania are comparable to those of other high-income countries. Current survival rates of children treated for cancer in Eastern European countries could be comparable to the best current standards contributing to better European survival rates of childhood cancer in general.

  17. Epigenetics targeted protein-vorinostat nanomedicine inducing apoptosis in heterogeneous population of primary acute myeloid leukemia cells including refractory and relapsed cases.

    Science.gov (United States)

    Chandran, Parwathy; Kavalakatt, Anu; Malarvizhi, Giridharan Loghanathan; Vasanthakumari, Divya Rani Vikraman Nair; Retnakumari, Archana Payickattu; Sidharthan, Neeraj; Pavithran, Keechilat; Nair, Shantikumar; Koyakutty, Manzoor

    2014-05-01

    Aberrant epigenetics play a key role in the onset and progression of acute myeloid leukemia (AML). Herein we report in silico modelling based development of a novel, protein-vorinostat nanomedicine exhibiting selective and superior anti-leukemic activity against heterogeneous population of AML patient samples (n=9), including refractory and relapsed cases, and three representative cell lines expressing CD34(+)/CD38(-) stem cell phenotype (KG-1a), promyelocytic phenotype (HL-60) and FLT3-ITD mutation (MV4-11). Nano-vorinostat having ~100nm size exhibited enhanced cellular uptake rendering significantly lower IC50 in AML cell lines and patient samples, and induced enhanced HDAC inhibition, oxidative injury, cell cycle arrest and apoptosis compared to free vorinostat. Most importantly, nanomedicine showed exceptional single-agent activity against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. Collectively, this epigenetics targeted nanomedicine appears to be a promising therapeutic strategy against various French-American-British (FAB) classes of AML. Through the use of a protein-vorinostat agent, exceptional single-agent activity was demonstrated against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. The studied epigenetics targeted nanomedicine approach is a promising therapeutic strategy against various French-American-British classes of acute myeloid leukemia. © 2014 Elsevier Inc. All rights reserved.

  18. The role of radiation therapy in childhood acute leukemia. A review from the viewpoint of basic and clinical radiation oncology

    International Nuclear Information System (INIS)

    Nozaki, Miwako

    2003-01-01

    Radiation therapy has been playing important roles in the treatment of childhood acute leukemia since the 1970s. The first is the preventive cranial irradiation for central nervous system therapy in acute lymphoblastic leukemia. The second is the total body irradiation as conditioning before bone marrow transplantation for children with acute myeloid leukemia in first remission and with acute lymphoblastic leukemia in second remission. Although some late effects have been reported, a part of them could be overcome by technical improvement in radiation and salvage therapy. Radiation therapy for children might have a successful outcome on a delicate balance between efficiencies and potential late toxicities. The role of radiation therapy for childhood acute leukemia was reviewed from the standpoint of basic and clinical radiation oncology in this paper. (author)

  19. Acute necrotizing encephalopathy of childhood: a fatal complication of swine flu

    International Nuclear Information System (INIS)

    Khan, M.R.; Maheshwari, P.K.; Haque, A.

    2010-01-01

    Acute necrotizing encephalopathy of childhood (ANEC) is a rare condition characterized by the presence of multifocal symmetrical brain lesions involving mainly thalami, brainstem, cerebellum and white matter. ANEC is a serious and life threatening complication of simple viral infections. We present a case of a young child who developed this condition with classical clinical and radiological findings consistent with ANEC, secondary to swine flu (H1N1). He needed ventilatory support and had profound motor and intellectual deficit on discharge. We report this case with aim of raising awareness about this fatal complication of swine flu which has become a global health care issue these days. (author)

  20. Childhood acute lymphoblastic leukemia presenting as ''cold'' lesions on bone scan: a report of two cases

    International Nuclear Information System (INIS)

    Caudle, R.J.; Crawford, A.H.; Gelfand, M.J.; Gruppo, R.A.

    1987-01-01

    ''Cold'' lesions on bone scan have been reported in a variety of disease processes, including infection, avascular necrosis, and cysts. We present two cases of children who presented with large ''cold'' areas on technetium bone scans and were treated initially for septic processes. Acute childhood leukemia frequently presents with bone or joint pain, fever, and elevation of the erythrocyte sedimentation rate. Although the diagnosis may be difficult if the characteristic clinical signs and laboratory findings are absent, the presence of anemia should alert the physician to the possibility of malignancy. Bone scanning provides a sensitive method of localizing pathology, but diagnosis requires biopsy or marrow aspiration

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

    DEFF Research Database (Denmark)

    Lund, Bendik; Åsberg, Ann; Heyman, Mats

    2011-01-01

    -cell disease (HR: 1.9, 95% CI: 1.01-3.7), Down syndrome (HR: 7.3, 95% CI: 3.6-14.9) and haematopoietic stem cell transplantation in CR1 (HR: 8.0, 95% CI: 3.3-19.5) were identified as independent risk factors for TRD. CONCLUSION: Several TRDs were potentially preventable and future efforts should be directed......BACKGROUND: In spite of major improvements in the cure rate of childhood acute lymphoblastic leukaemia (ALL), 2-4% of patients still die from treatment related complications. PROCEDURE: We investigated the pattern of treatment related deaths (TRDs) and possible risk factors in the NOPHO ALL-92...

  2. Ophthalmic evaluation of long-term survivors of childhood acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Weaver, R.G. Jr.; Chauvenet, A.R.; Smith, T.J.; Schwartz, A.C.

    1986-01-01

    Thirty-four long-term survivors of childhood acute lymphoblastic leukemia (ALL) underwent comprehensive ophthalmic examinations to detect retinopathy or other ocular sequelae. Sixteen of the 34 patients received whole brain radiation (greater than or equal to 2400 rad). All 18 patients in the non-radiated group had normal eye examinations, while 4 of 16 in the radiated group had ocular abnormalities. None of the ocular abnormalities could be definitely attributed to radiation and all patients had normal visual acuity. No radiation retinopathy was found in either group

  3. Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

    Science.gov (United States)

    2014-08-26

    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); Blastic Phase Chronic Myelogenous Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Secondary Acute Myeloid Leukemia; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma

  4. A case of acute spinal subdural hematoma with subarachnoid hemorrhage: Rapid spontaneous remission, relapse, and complete resolution

    Directory of Open Access Journals (Sweden)

    Michito Namekawa

    2017-06-01

    In addition to rostrocaudal spreading of bloody components in the subdural space, rupture of the hematoma into the subarachnoid space must have released pressure, compressing the spinal cord. In this case report, we also describe the serial MRI studies and note the limitations of the resolution of spinal MRI in the acute phase.

  5. Effect of Prophylactic Cranial Irradiation in Acute Lymphoblastic Leukemia in Children

    International Nuclear Information System (INIS)

    Kim, Il Han; Choi, Doo Ho; Kim, Jong Hoon; Ha, Sung Whan; Park, Charn Il; Ahn, Hyo Seop

    1989-01-01

    CNS prophylaxis with 18 or 24 Gy cranial irradiation plus intrathecal methotrexate was given to 134 childhood acute lymphoblastic leukemia patients who had got bone marrow remission(M1) after remission induction chemotherapy from August 1979 to December 1986. The rate of initial total CNS relapse was 14.2%(19/134), the rate of isolated CNS relapse was 5.2%(7/134), and the rate of CNS relapse concomitantly combined with bone marrow relapse or testicular relapse was 9%(12/134). Male sex or older age was associated with higher CNS relapses and the initial peripheral leukocyte count over 50,000/ul had higher relapse rate. Relapse with radiation dose of 18 Gy was somewhat lower than that with 24 Gy. Within 4 years after CNS prophylaxis occurred 89% of the total CNS relapses, 100% of the isolated CNS relapses, and 83% of the combined CNS relapses. Adjusted to exposed cases to risk of CNS relapse, the total CNS relapse rate was 11.9% during maintenance chemotherapy and 4.9% after maintenance chemotherapy

  6. A Phase I Study of CPI-613 in Combination with High-Dose Cytarabine and Mitoxantrone for Relapsed or Refractory Acute Myeloid Leukemia.

    Science.gov (United States)

    Pardee, Timothy S; Anderson, Rebecca G; Pladna, Kristin M; Isom, Scott; Ghiraldeli, Lais P; Miller, Lance D; Chou, Jeff W; Jin, Guangxu; Zhang, Wei; Ellis, Leslie R; Berenzon, Dmitriy; Howard, Dianna S; Hurd, David D; Manuel, Megan; Dralle, Sarah; Lyerly, Susan; Powell, Bayard L

    2018-05-01

    Purpose: CPI-613, a lipoate analogue that inhibits pyruvate dehydrogenase (PDH) and α-ketogluterate dehydrogenase (KGDH), has activity in patients with myeloid malignancies. This study explored the role of mitochondrial metabolism in chemotherapy response and determined the MTD, efficacy, and safety of CPI-613 combined with high-dose cytarabine and mitoxantrone in patients with relapsed or refractory acute myeloid leukemia. Experimental Design: The role of mitochondrial response to chemotherapy was assessed in cell lines and animal models. A phase I study of CPI-613 plus cytarabine and mitoxantrone was conducted in patients with relapsed or refractory AML. Results: Exposure to chemotherapy induced mitochondrial oxygen consumption that depended on PDH. CPI-613 sensitized AML cells to chemotherapy indicating that mitochondrial metabolism is a source of resistance. Loss of p53 did not alter response to CPI-613. The phase I study enrolled 67 patients and 62 were evaluable for response. The overall response rate was 50% (26CR+5CRi/62). Median survival was 6.7 months. In patients over 60 years old, the CR/CRi rate was 47% (15/32) with a median survival of 6.9 months. The response rate for patients with poor-risk cytogenetics also was encouraging with 46% (11/24 patients) achieving a CR or CRi. RNA sequencing analysis of a subset of baseline bone marrow samples revealed a gene expression signature consistent with the presence of B cells in the pretreatment marrow of responders. Conclusions: The addition of CPI-613 to chemotherapy is a promising approach in older patients and those with poor-risk cytogenetics. Clin Cancer Res; 24(9); 2060-73. ©2018 AACR . ©2018 American Association for Cancer Research.

  7. Primary segmental omental infarction as a rare cause of acute abdominal pain in childhood

    Directory of Open Access Journals (Sweden)

    N.F. Tepeneu

    2018-01-01

    Full Text Available Introduction: Primary omental infarction (POI has a low incidence worldwide, with most cases occurring in adults. This condition is rarely considered in the differential diagnosis of acute abdominal pain in childhood. Material and methods: We present 2 cases of omental infarction in an obese 8-year-old boy and a 5-year-old boy who presented with acute abdominal pain in the right abdomen. Both patients were initially treated with intravenous fluids and analgesics with no improvement. Abdominal ultrasound of the first patient showed free intraperitoneal fluid, meteorism and distended bowel loops. The appendix was not visualized. With a presumptive clinical diagnosis of appendicitis the child underwent laparotomy.On entering the peritoneal cavity an omental infarction was seen and a portion of the omentum was resected. Appendectomy was performed.The second patient presented with acute abdominal pain in the right upper quadrant, which started 2 days before. There was a history of possible abdominal trauma about 3 weeks earlier. The patient had repeated ultrasound examinations and a CT scan of the abdomen which showed a omental infarction. He underwent laparoscopy and resection of the omental infarction, as well as incidental appendectomy. Results: The postoperative period was uneventful. The first patient was discharged on day 3, the second patient on day 4 after surgery. Histology showed a normal vermiform appendix and an omental infarction in both cases. Conclusion and discussion: Since the omental infarction as etiology of acute abdominal pain is uncommon in children, we emphasize the importance of accurate diagnosis and appropriate treatment of omental infarction. Keywords: Primary segmental omental infarction (POI, Appendicitis, Childhood

  8. Cranial radiotherapy predisposes to abdominal adiposity in survivors of childhood acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Siviero-Miachon, Adriana Aparecida; Spinola-Castro, Angela Maria; Lee, Maria Lúcia de Martino; Andreoni, Solange; Geloneze, Bruno; Lederman, Henrique; Guerra-Junior, Gil

    2013-01-01

    Advances in treatment of acute lymphocytic leukemia increased the likelihood of developing late treatment-associated effects, such as abdominal adiposity, increasing the risk of cardiovascular disease in this population. Cranial radiotherapy is one of the factors that might be involved in this process. The aim of this study was to determine the effect of cranial radiotherapy on adiposity indexes in survivors of acute lymphocytic leukemia. A comparative cross-sectional study of 56 acute lymphocytic leukemia survivors, chronological age between 15 and 24 years, assigned into two groups according to the exposure to cranial radiotherapy (25 irradiated and 31 non-irradiated), assessed according to body fat (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, and insulin resistance. Cranial radiotherapy increased body fat and abdominal adipose tissue and altered lipid panel. Yet, lipids showed no clinical relevance so far. There were significantly more obese patients among those who received cranial radiotherapy (52% irradiated versus 22.6% non-irradiated), based on dual energy X-ray absorptiometry body fat measurements. Nonetheless, no association was observed between cranial radiotherapy and body mass index, waist circumference, waist-to-height ratio or insulin resistance. Adolescent and young adult survivors of childhood acute lymphocytic leukemia showed an increase in body fat and an alteration of fat distribution, which were related to cranial radiotherapy. Fat compartment modifications possibly indicate a disease of adipose tissue, and cranial radiotherapy imports in this process

  9. Molecular signatures in childhood acute leukemia and their correlations to expression patterns in normal hematopoietic subpopulations.

    Science.gov (United States)

    Andersson, Anna; Olofsson, Tor; Lindgren, David; Nilsson, Björn; Ritz, Cecilia; Edén, Patrik; Lassen, Carin; Råde, Johan; Fontes, Magnus; Mörse, Helena; Heldrup, Jesper; Behrendtz, Mikael; Mitelman, Felix; Höglund, Mattias; Johansson, Bertil; Fioretos, Thoas

    2005-12-27

    Global expression profiles of a consecutive series of 121 childhood acute leukemias (87 B lineage acute lymphoblastic leukemias, 11 T cell acute lymphoblastic leukemias, and 23 acute myeloid leukemias), six normal bone marrows, and 10 normal hematopoietic subpopulations of different lineages and maturations were ascertained by using 27K cDNA microarrays. Unsupervised analyses revealed segregation according to lineages and primary genetic changes, i.e., TCF3(E2A)/PBX1, IGH@/MYC, ETV6(TEL)/RUNX1(AML1), 11q23/MLL, and hyperdiploidy (>50 chromosomes). Supervised discriminatory analyses were used to identify differentially expressed genes correlating with lineage and primary genetic change. The gene-expression profiles of normal hematopoietic cells were also studied. By using principal component analyses (PCA), a differentiation axis was exposed, reflecting lineages and maturation stages of normal hematopoietic cells. By applying the three principal components obtained from PCA of the normal cells on the leukemic samples, similarities between malignant and normal cell lineages and maturations were investigated. Apart from showing that leukemias segregate according to lineage and genetic subtype, we provide an extensive study of the genes correlating with primary genetic changes. We also investigated the expression pattern of these genes in normal hematopoietic cells of different lineages and maturations, identifying genes preferentially expressed by the leukemic cells, suggesting an ectopic activation of a large number of genes, likely to reflect regulatory networks of pathogenetic importance that also may provide attractive targets for future directed therapies.

  10. Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Ng, O H; Erbilgin, Y; Firtina, S; Celkan, T; Karakas, Z; Aydogan, G; Turkkan, E; Yildirmak, Y; Timur, C; Zengin, E; Dongen, J J M van; Staal, F J T; Ozbek, U; Sayitoglu, M

    2014-01-01

    WNT signaling has been implicated in the regulation of hematopoietic stem cells and plays an important role during T-cell development in thymus. Here we investigated WNT pathway activation in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. To evaluate the potential role of WNT signaling in T-cell leukomogenesis, we performed expression analysis of key components of WNT pathway. More than 85% of the childhood T-ALL patients showed upregulated β-catenin expression at the protein level compared with normal human thymocytes. The impact of this upregulation was reflected in high expression of known target genes (AXIN2, c-MYC, TCF1 and LEF). Especially AXIN2, the universal target gene of WNT pathway, was upregulated at both mRNA and protein levels in ∼40% of the patients. When β-CATENIN gene was silenced by small interfering RNA, the cancer cells showed higher rates of apoptosis. These results demonstrate that abnormal WNT signaling activation occurs in a significant fraction of human T-ALL cases independent of known T-ALL risk factors. We conclude that deregulated WNT signaling is a novel oncogenic event in childhood T-ALL

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

    International Nuclear Information System (INIS)

    Roux, P.

    1987-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Roux, P

    1987-01-01

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

  13. [Effects of birth order, maternal abortion and mode of delivery on childhood acute leukemia risk: a meta-analysis].

    Science.gov (United States)

    Zou, Guobin; Sha, Xia

    2014-03-01

    To evaluate the associations between birth order, maternal abortion and mode of delivery and childhood acute leukemia risk. Multiple electronic databases were searched to identify relevant studies up to March 2013 using the search terms "childhood leukemia", "acute lymphoblastic leukemia", "acute myeloid leukemia","birth order", "abortion", "miscarriage", "cesarean", "birth characteristics" and "prenatal risk factor". Data from cohort and case-control studies were analyzed using the Stata software. Twenty-three studies were included in this meta-analysis according to the selection criteria. No significant associations were identified for birth order and mode of delivery (birth order = 2: OR = 0.97, 95%CI: 0.89-1.05; birth order = 3: OR = 1.00, 95%CI: 0.91-1.11; birth order ≥ 4: OR = 1.02, 95%CI: 0.87-1.20; mode of delivery: OR = 1.05, 95%CI: 0.96-1.15). However, there was a significant association between maternal abortion and childhood acute leukemia risk (spontaneous abortion: OR = 1.21, 95%CI: 1.05-1.41; induced abortion: OR = 1.23, 95%CI: 1.07-1.43). Furthermore, the stratified analysis by disease subtypes showed that spontaneous and induced abortions were significantly associated with the risks of childhood acute myeloid leukemia (OR = 1.71, 95%CI: 1.09-2.70) and acute lymphoblastic leukemia (OR = 1.23, 95%CI: 1.05-1.42), respectively. This meta-analysis revealed that maternal abortion might contribute to the childhood acute leukemia risk.

  14. 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.

  15. Extramedullary leukemia in children with acute myeloid leukemia

    DEFF Research Database (Denmark)

    Støve, Heidi Kristine; Sandahl, Julie Damgaard; Abrahamsson, Jonas

    2017-01-01

    BACKGROUND: The prognostic significance of extramedullary leukemia (EML) in childhood acute myeloid leukemia is not clarified. PROCEDURE: This population-based study included 315 children from the NOPHO-AML 2004 trial. RESULTS: At diagnosis, 73 (23%) patients had EML: 39 (12%) had myeloid sarcoma...... the OS. No patients relapsed at the primary site of the myeloid sarcoma despite management without radiotherapy....

  16. Recent advances in the diagnosis and management of childhood acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Eun Sun Yoo

    2011-03-01

    Full Text Available Since the successful introduction of all-trans-retinoic acid (ATRA and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than 90%, and the long-term survival rate is 70&#8210;89%. Moreover, arsenic trioxide (ATO, which was introduced for APL treatment in 1994, resulted in excellent remission rates in relapsed patients with APL, and more recently, several clinical studies have been designed to explore its role in initial therapy either alone or in combination with ATRA. APL is a rare disease in children and is frequently associated with hyperleukocytosis, which is a marker for higher risk of relapse and an increased incidence of microgranular morphology. The frequency of occurrence of the promyelocytic leukemia/ retinoic acid receptor-alpha (PML/RAR?#6752;isoforms bcr 2 and bcr 3 is higher in children than in adults. Although recent clinical studies have reported comparable long-term survival rates in patients with APL, therapy for APL in children is challenging because of the risk of early death and the potential long-term cardiac toxicity resulting from the need to use high doses of anthracyclines. Additional prospective, randomized, large clinical trials are needed to address several issues in pediatric APL and to possibly minimize or eliminate the need for chemotherapy by combining ATRA and ATO. In this review article, we discuss the molecular pathogenesis, diagnostic progress, and most recent therapeutic advances in the treatment of children with APL.

  17. Affective temperaments are associated with specific clusters of symptoms and psychopathology: a cross-sectional study on bipolar disorder inpatients in acute manic, mixed, or depressive relapse.

    Science.gov (United States)

    Iasevoli, Felice; Valchera, Alessandro; Di Giovambattista, Emanuela; Marconi, Massimo; Rapagnani, Maria Paola; De Berardis, Domenico; Martinotti, Giovanni; Fornaro, Michele; Mazza, Monica; Tomasetti, Carmine; Buonaguro, Elisabetta F; Di Giannantonio, Massimo; Perugi, Giulio; de Bartolomeis, Andrea

    2013-11-01

    The aim of this study was to assess whether different affective temperaments could be related to a specific mood disorder diagnosis and/or to different therapeutic choices in inpatients admitted for an acute relapse of their primary mood disorder. Hundred and twenty-nine inpatients were consecutively assessed by means of the Structured and Clinical Interview for axis-I disorders/Patient edition and by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego auto-questionnaire, Young Mania Rating Scale, Hamilton Scale for Depression and for Anxiety, Brief Psychiatry Rating Scale, Clinical Global impression, Drug Attitude Inventory, Barratt Impulsiveness Scale, Toronto Alexithymia Scale, and Symptoms Checklist-90 items version, along with records of clinical and demographic data. The following prevalence rates for axis-I mood diagnoses were detected: bipolar disorder type I (BD-I, 28%), type II (31%), type not otherwise specified (BD-NOS, 33%), major depressive disorder (4%), and schizoaffective disorder (4%). Mean scores on the hyperthymic temperament scale were significantly higher in BD-I and BD-NOS, and in mixed and manic acute states. Hyperthymic temperament was significantly more frequent in BD-I and BD-NOS patients, whereas depressive temperament in BD-II ones. Hyperthymic and irritable temperaments were found more frequently in mixed episodes, while patients with depressive and mixed episodes more frequently exhibited anxious and depressive temperaments. Affective temperaments were associated with specific symptom and psychopathology clusters, with an orthogonal subdivision between hyperthymic temperament and anxious/cyclothymic/depressive/irritable temperaments. Therapeutic choices were often poorly differentiated among temperaments and mood states. Cross-sectional design; sample size. Although replication studies are needed, current results suggest that temperament-specific clusters of symptoms severity and psychopathology domains could be

  18. CD19 CAR-T cell therapy for relapsed/refractory acute lymphoblastic leukemia: factors affecting toxicities and long-term efficacies.

    Science.gov (United States)

    Zhang, Li-Na; Song, Yongping; Liu, Delong

    2018-03-15

    The prognosis of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) remains dismal even at this day and age. With salvage chemotherapy, only 29% (range 18 to 44%) of the patients with R/R ALL can be induced into complete remission (CR), with a median overall survival (OS) of 4 months (range 2-6 months). Blinatumomab and inotuzumab ozogamycin (IO) are immunotherapeutic agents that increased CR to 80% and extended survival to 7.7 months in this high-risk population of patients. In the last few years, chimeric antigen receptor (CAR)--engineered T cells have led to major progress in cancer immunotherapy. CD-19 CAR-T cells have been recently approved for high-risk R/R ALL and lymphoma. The data from long-term follow-up of a single-center phase I study of 19-28z CAR-T cell therapy for adult R/R ALL were just published. At the same time, a multicenter phase II study of 19-41BB CAR-T cell therapy for children and young adults with R/R B cell ALL was also published. The two studies provided fresh information with long-term follow-up. This research highlight analyzed the data and proposed future perspectives for further investigation in this rapidly evolving field.

  19. Long-term hearing outcomes after recurrent acute otitis media during early childhood.

    Science.gov (United States)

    Krakau, Mattias; Dagöö, Britta Rynnel; Hellström, Sten; Granath, Anna

    2017-12-01

    To survey long-term hearing outcomes and middle ear pathology in a 30-year follow-up in individuals with onset of recurrent acute otitis media (rAOM) before three years of age. 28 adults, aged 30.1-31.8 years, who originally - at the age of 12-32 months - participated in a study on rAOM between 1979 and 1983, were re-examined regarding self-reported ear problems, current tympanic membrane changes and audiology. Thirteen subjects had suffered from rAOM during early childhood and 15 subjects served as a control group. Recurrent acute otitis media subjects reported hearing problems comparable to those of the controls. Pure tone audiometry, at 125-8000 Hz, did not differ between groups. The rAOM group had a trend for impaired high-frequency (9000-14,000 Hz) threshold levels (9000-14,000 Hz); implying that their cochlear function seemed to have deteriorated. Adults, who suffered from recurrent acute otitis media as infants, did not show any clinically significant hearing loss for pure tone audiometry when compared to controls, but there was a trend for impaired results regarding extended high frequency audiometry (9-14 kHz). Children suffering from rAOM will be at low risk of developing hearing loss and severe middle ear disease.

  20. Impact of Childhood Nutritional Status on Pathogen Prevalence and Severity of Acute Diarrhea.

    Science.gov (United States)

    Tickell, Kirkby D; Pavlinac, Patricia B; John-Stewart, Grace C; Denno, Donna M; Richardson, Barbra A; Naulikha, Jaqueline M; Kirera, Ronald K; Swierczewski, Brett E; Singa, Benson O; Walson, Judd L

    2017-11-01

    Children with acute and chronic malnutrition are at increased risk of morbidity and mortality following a diarrheal episode. To compare diarrheal disease severity and pathogen prevalence among children with and without acute and chronic malnutrition, we conducted a cross-sectional study of human immunodeficiency virus-uninfected Kenyan children aged 6-59 months, who presented with acute diarrhea. Children underwent clinical and anthropometric assessments and provided stool for bacterial and protozoal pathogen detection. Clinical and microbiological features were compared using log binomial regression among children with and without wasting (mid-upper arm circumference ≤ 125 mm) or stunting (height-for-age z score ≤ -2). Among 1,363 children, 7.0% were wasted and 16.9% were stunted. After adjustment for potential confounders, children with wasting were more likely than nonwasted children to present with at least one Integrated Management of Childhood Illness danger sign (adjusted prevalence ratio [aPR]: 1.3, 95% confidence interval [CI]: 1.0 to 1.5, P = 0.05), severe dehydration (aPR: 2.4, 95% CI: 1.5 to 3.8, P malnutrition which may be explained by a delay in care-seeking or diminished immune response to infection. Combating social determinants and host risk factors associated with severe disease, rather than specific pathogens, may reduce the disparities in poor diarrhea-associated outcomes experienced by malnourished children.

  1. Contextual factors associated with health care service utilization for children with acute childhood illnesses in Nigeria.

    Directory of Open Access Journals (Sweden)

    Sulaimon T Adedokun

    Full Text Available To examine the independent contribution of individual, community and state-level factors to health care service utilization for children with acute childhood illnesses in Nigeria.The study was based on secondary analyses of cross-sectional population-based data from the 2013 Nigeria Demographic and Health Survey (DHS. Multilevel logistic regression models were applied to the data on 6,427 under-five children who used or did not use health care service when they were sick (level 1, nested within 896 communities (level 2 from 37 states (level 3.About one-quarter of the mothers were between 15 and 24 years old and almost half of them did not have formal education (47%. While only 30% of the children utilized health service when they were sick, close to 67% lived in the rural area. In the fully adjusted model, mothers with higher education attainment (Adjusted odds ratio [aOR] = 1.63; 95% credible interval [CrI] = 1.31-2.03, from rich households (aOR = 1.76; 95% CrI = 1.35-2.25, with access to media (radio, television or magazine (aOR = 1.18; 95% CrI = 1.08-1.29, and engaging in employment (aOR = 1.18; 95% CrI = 1.02-1.37 were significantly more likely to have used healthcare services for acute childhood illnesses. On the other hand, women who experienced difficulty getting to health facilities (aOR = 0.87; 95% CrI = 0.75-0.99 were less likely to have used health service for their children.Our findings highlight that utilization of healthcare service for acute childhood illnesses was influenced by not only maternal factors but also community-level factors, suggesting that public health strategies should recognise this complex web of individual composition and contextual composition factors to guide provision of healthcare services. Such interventions could include: increase in female school enrolment, provision of interest-free loans for small and medium scale enterprises, introduction of mobile clinics and establishment of more primary health care

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    To explore the DNA incorporation of 6-thioguanine nucleotide levels (DNA-6TGN) during 6-mercaptopurine (6MP) therapy of childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma (NHL) and its relation to erythrocyte levels of their metabolites: 6-thioguanine-nucleotides (E-6TGN...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those e...

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

    DEFF Research Database (Denmark)

    Borst, Louise; Wallerek, Sandra; Dalhoff, Kim

    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...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  7. Granulocyte colony stimulating factor priming chemotherapy is more effective than standard chemotherapy as salvage therapy in relapsed acute myeloid leukemia.

    Science.gov (United States)

    Shen, Ying; He, Aili; Wang, Fangxia; Bai, Ju; Wang, Jianli; Zhao, Wanhong; Zhang, Wanggang; Cao, Xingmei; Chen, Yinxia; Liu, Jie; Ma, Xiaorong; Chen, Hongli; Feng, Yuandong; Yang, Yun

    2017-12-29

    To improve the complete remission (CR) rate of newly diagnosed acute myeloid leukemia (AML) patients and alleviate the severe side effects of double induction chemotherapy, we combined a standard regimen with granulocyte colony-stimulating factor (G-CSF) priming chemotherapy to compose a new double induction regimen for AML patients who failed to achieve CR after the first course. Ninety-seven patients with AML who did not achieve CR after the first course of standard chemotherapy were enrolled. Among them, 45 patients received G-CSF priming combined with low-dose chemotherapy during days 20-22 of the first course of chemotherapy, serving as priming group, 52 patients were administered standard chemotherapy again, serving as control group. Between the two groups there were no differences in the French-American-British (FAB) classification, risk status, the first course of chemotherapy, blood cell count or blasts percentage of bone marrow before the second course. But the CR rate was significantly higher and the adverse effect was much lower in the priming group than the control group. Cox multivariate regression analysis showed that WBC level before the second course and the selection of the second chemotherapy regimen were two independent factors for long survival of patients. These results elucidate that standard chemotherapy followed by G-CSF priming new double induction chemotherapy is an effective method for AML patients to improve CR rate and reduce adverse effects. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  8. Sarcoma granulocítico multicêntrico como recidiva de leucemia mieloide aguda Multicentric granulocytic sarcoma as relapse of acute myelogenous leukemia

    Directory of Open Access Journals (Sweden)

    Taciana G. S. Aguiar

    2009-01-01

    Full Text Available Sarcoma granulocítico (SG é um tumor sólido extramedular, constituído por células precursoras de granulócitos. É geralmente associado a leucemia mieloide aguda ou raramente a outras desordens mieloproliferativas. O tumor geralmente ocorre precedendo uma leucemia mieloide aguda, durante o seu curso ou após a remissão ter sido alcançada. O prognóstico é pobre e tem como principais modalidades terapêuticas a quimioterapia e a radioterapia. Relata- se um caso de SG multicêntrico, de evolução rápida, com acometimento difuso de pele, mamas, gânglios linfáticos, tecido celular subcutâneo e líquor, em mulher de 45 anos, fora de tratamento para leucemia mieloide aguda e em remissão hematológica há 18 meses. A paciente apresentava dor intensa em membro inferior direito há uma semana e estava em anticoagulação oral há seis meses por trombose venosa profunda neste membro. Diagnosticado o SG, a paciente foi tratada com radioterapia e quimioterapia com boa resposta. Após três meses de seguimento, em vigência do tratamento quimioterápico, evoluiu com recidiva do SG neste membro, associado ao acometimento das mamas e posteriormente do sistema nervoso central, evoluindo para óbito em aplasia e sepses.Granulocytic sarcoma is an extramedullary solid tumor consisting of immature granulocytic cells. It is often associated with acute myelogenous leukemia and more rarely with other myeloproliferative disorders. The tumor generally occurs before acute myeloid leukemia, during its course or after disease remission. It has a poor prognosis with the main therapeutic options being chemotherapy and radiotherapy. A multicentric accelerated case of granulocytic sarcoma of a 45- year- old woman with diffuse skin, breast, lymphatic ganglia and subcutaneous tissue presentations no longer undergoing treatment for acute myeloid leukemia and in hematologic remission for 18 months is reported. The patient presented with severe pain of right lower

  9. Living on a farm, contact with farm animals and pets, and childhood acute lymphoblastic leukemia: pooled and meta-analyses from the Childhood Leukemia International Consortium.

    Science.gov (United States)

    Orsi, Laurent; Magnani, Corrado; Petridou, Eleni T; Dockerty, John D; Metayer, Catherine; Milne, Elizabeth; Bailey, Helen D; Dessypris, Nick; Kang, Alice Y; Wesseling, Catharina; Infante-Rivard, Claire; Wünsch-Filho, Victor; Mora, Ana M; Spector, Logan G; Clavel, Jacqueline

    2018-04-16

    The associations between childhood acute lymphoblastic leukemia (ALL) and several factors related to early stimulation of the immune system, that is, farm residence and regular contacts with farm animals (livestock, poultry) or pets in early childhood, were investigated using data from 13 case-control studies participating in the Childhood Leukemia International Consortium. The sample included 7847 ALL cases and 11,667 controls aged 1-14 years. In all studies, the data were obtained from case and control parents using standardized questionnaires. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Contact with livestock in the first year of life was inversely associated with ALL (OR = 0.65, 95% CI: 0.50, 0.85). Inverse associations were also observed for contact with dogs (OR = 0.92, 95% CI: 0.86, 0.99) and cats (OR = 0.87, 95% CI: 0.80, 0.94) in the first year of life. There was no evidence of a significant association with farm residence in the first year of life. The findings of these large pooled and meta-analyses add additional evidence to the hypothesis that regular contact with animals in early childhood is inversely associated with childhood ALL occurrence which is consistent with Greaves' delayed infection hypothesis. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  10. 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...... resistant to MTX at diagnosis may allow for tailoring novel treatment strategies to individual leukemia patients....... leukemia (ALL). However, drug resistance phenomena pose major obstacles to efficacious ALL chemotherapy. Moreover, clinically relevant molecular mechanisms underlying chemoresistance remain largely obscure. Several alterations in MTX metabolism, leading to impaired accumulation of this cytotoxic agent...... in tumor cells, have been classified as determinants of MTX resistance. However, the relation between MTX resistance and long-term clinical outcome of ALL has not been shown previously. METHODS: We have collected clinical data for 235 childhood ALL patients, for whom samples taken at the time of diagnosis...

  11. Brain sarcoma of meningeal origin after cranial irradiation in childhood acute lymphocytic leukemia. Case report

    International Nuclear Information System (INIS)

    Tiberin, P.; Maor, E.; Zaizov, R.; Cohen, I.J.; Hirsch, M.; Yosefovich, T.; Ronen, J.; Goldstein, J.

    1984-01-01

    The authors report their experience with an unusual case of intracerebral sarcoma of meningeal cell origin in an 8 1/2-year-old girl. This tumor occurred 6 1/2 years after cranial irradiation at relatively low dosage (2200 rads) had been delivered to the head in the course of a multimodality treatment for acute lymphocytic leukemia. The tumor recurred approximately 10 months after the first surgical intervention. Macroscopic total excision of the recurrent growth followed by whole-brain irradiation (4500 rads) failed to eradicate it completely and local recurrence prompted reoperation 18 months later. This complication of treatment in long-term childhood leukemia survivors is briefly discussed, as well as the pathology of meningeal sarcomas

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

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Scrideli

    2001-09-01

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

  13. 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

  14. Exposure to professional pest control treatments and the risk of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Bailey, Helen D; Armstrong, Bruce K; de Klerk, Nicholas H; Fritschi, Lin; Attia, John; Scott, Rodney J; Smibert, Elizabeth; Milne, Elizabeth

    2011-10-01

    Previous studies suggest that exposure to pesticides increases the risk of childhood acute lymphoblastic leukemia (ALL). The aim of this analysis was to investigate whether professional pest treatments in or around the home before birth or during childhood increased the risk of childhood ALL. Data from 388 cases and 870 frequency-matched controls were analyzed using unconditional logistic regression, adjusting for study matching variables and potential confounders, to calculate odds ratios (ORs). A meta-analysis of our findings with the published findings of previous studies was also conducted. The ORs for any professional pest control treatments were 1.19 (95% CI 0.83, 1.69) in the year before pregnancy, 1.30 (95% CI 0.86, 1.97) during pregnancy and 1.24 (95% CI 0.93, 1.65) for those done after the child's birth. The ORs for exposure after birth were highest when it occurred between the ages of two and three years. ORs were elevated for termite treatments before birth. ORs were higher for pre-B than T cell ALL and for t(12;21) (ETV6-Runx-1) than other cytogenetic sub-types. The pooled OR from a meta-analysis of our study with three previous studies of professional pest control treatments during pregnancy was 1.37 (95% CI 1.00, 1.88). Our results, and those of our meta-analysis, provide some evidence of a modestly increased risk of ALL for professional pest control treatments done during the index pregnancy and possibly in the child's early years. The analysis of pooled data from international collaborations may provide more certainty regarding these potentially important associations. Copyright © 2011 UICC.

  15. The association of folate pathway and DNA repair polymorphisms with susceptibility to childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Goričar, Katja; Erčulj, Nina; Faganel Kotnik, Barbara; Debeljak, Maruša; Hovnik, Tinka; Jazbec, Janez; Dolžan, Vita

    2015-05-15

    Genetic factors may play an important role in susceptibility to childhood acute lymphoblastic leukemia (ALL). The aim of our study was to evaluate the associations of genetic polymorphisms in folate pathway and DNA repair genes with susceptibility to ALL. In total, 121 children with ALL and 184 unrelated healthy controls of Slovenian origin were genotyped for 14 polymorphisms in seven genes of folate pathway, base excision repair and homologous recombination repair (TYMS, MTHFR, OGG1, XRCC1, NBN, RAD51, and XRCC3). In addition, the exon 6 of NBN was screened for the presence of mutations using denaturing high performance liquid chromatography. Twelve polymorphisms were in Hardy-Weinberg equilibrium in controls and their genotype frequencies were in agreement with those reported in other Caucasian populations. Among the investigated polymorphisms and mutations, NBN Glu185Gln significantly decreased susceptibility to B-cell ALL (p=0.037), while TYMS 3R allele decreased susceptibility to T-cell ALL (p=0.011). Moreover, significantly decreased susceptibility to ALL was observed for MTHFR TA (p=0.030) and RAD51 GTT haplotypes (p=0.016). Susceptibility to ALL increased with the increasing number of risk alleles (ptrend=0.007). We also observed significant influence of hOGG-RAD51 and NBN-RAD51 interactions on susceptibility to ALL. Our results suggest that combination of several polymorphisms in DNA repair and folate pathways may significantly affect susceptibility to childhood ALL. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  18. Childhood acute non-traumatic coma: aetiology and challenges in management in resource-poor countries of Africa and Asia.

    Science.gov (United States)

    Gwer, Samson; Chacha, Clifford; Newton, Charles R; Idro, Richard

    2013-08-01

    This review examines the best available evidence on the aetiology of childhood acute non-traumatic coma in resource-poor countries (RPCs), discusses the challenges associated with management, and explores strategies to address them. Publications in English and French which reported on studies on the aetiology of childhood non-traumatic coma in RPCs are reviewed. Primarily, the MEDLINE database was searched using the keywords coma, unconsciousness, causality, aetiology, child, malaria cerebral, meningitis, encephalitis, Africa, Asia, and developing countries. 14 records were identified for inclusion in the review. Cerebral malaria (CM) was the commonest cause of childhood coma in most of the studies conducted in Africa. Acute bacterial meningitis (ABM) was the second most common known cause of coma in seven of the African studies. Of the studies in Asia, encephalitides were the commonest cause of coma in two studies in India, and ABM was the commonest cause of coma in Pakistan. Streptococcus pneumoniae was the most commonly isolated organism in ABM. Japanese encephalitis, dengue fever and enteroviruses were the viral agents most commonly isolated. Accurate diagnosis of the aetiology of childhood coma in RPCs is complicated by overlap in clinical presentation, limited diagnostic resources, disease endemicity and co-morbidity. For improved outcomes, studies are needed to further elucidate the aetiology of childhood coma in RPCs, explore simple and practical diagnostic tools, and investigate the most appropriate specific and supportive interventions to manage and prevent infectious encephalopathies.

  19. Dose study of the multikinase inhibitor, LY2457546, in patients with relapsed acute myeloid leukemia to assess safety, pharmacokinetics, and pharmacodynamics

    International Nuclear Information System (INIS)

    Wacheck, Volker; Lahn, Michael; Dickinson, Gemma; Füreder, Wolfgang; Meyer, Renata; Herndlhofer, Susanne; Füreder, Thorsten; Dorfner, Georg; Pillay, Sada; André, Valérie; Burkholder, Timothy P; Akunda, Jacqueline K; Flye-Blakemore, Leann; Van Bockstaele, Dirk; Schlenk, Richard F; Sperr, Wolfgang R; Valent, Peter

    2011-01-01

    Acute myeloid leukemia (AML) is a life-threatening malignancy with limited treatment options in chemotherapy-refractory patients. A first-in-human dose study was designed to investigate a safe and biologically effective dose range for LY2457546, a novel multikinase inhibitor, in patients with relapsed AML. In this nonrandomized, open-label, dose escalation Phase I study, LY2457546 was administered orally once a day. Safety, pharmacokinetics, changes in phosphorylation of target kinases in AML blasts, and risk of drug–drug interactions (DDI) were assessed. Five patients were treated at the starting and predicted minimal biologically effective dose of 50 mg/day. The most commonly observed adverse events were febrile neutropenia, epistaxis, petechiae, and headache. The majority of adverse events (81%) were Grade 1 or 2. One patient had generalized muscle weakness (Grade 3), which was deemed to be a dose-limiting toxicity. Notably, the pharmacokinetic profile of LY2457546 showed virtually no elimination of LY2457546 within 24 hours, and thus prevented further dose escalation. No significant DDI were observed. Ex vivo flow cytometry studies showed downregulation of the phosphoproteins, pcKIT, pFLT3, and pS6, in AML blasts after LY2457546 administration. No medically relevant responses were observed in the five treated patients. No biologically effective dose could be established for LY2457546 in chemotherapy-resistant AML patients. Lack of drug clearance prevented safe dose escalation, and the study was terminated early. Future efforts should be made to develop derivatives with a more favorable pharmacokinetic profile

  20. A phase I trial of vorinostat and alvocidib in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2.

    Science.gov (United States)

    Holkova, Beata; Supko, Jeffrey G; Ames, Matthew M; Reid, Joel M; Shapiro, Geoffrey I; Perkins, Edward Brent; Ramakrishnan, Viswanathan; Tombes, Mary Beth; Honeycutt, Connie; McGovern, Renee M; Kmieciak, Maciej; Shrader, Ellen; Wellons, Martha D; Sankala, Heidi; Doyle, Austin; Wright, John; Roberts, John D; Grant, Steven

    2013-04-01

    This phase I study was conducted to identify the maximum-tolerated dose (MTD) of alvocidib when combined with vorinostat in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2. Secondary objectives included investigating the pharmacokinetic and pharmacodynamic effects of the combination. Patients received vorinostat (200 mg orally, three times a day, for 14 days) on a 21-day cycle, combined with 2 different alvocidib administration schedules: a 1-hour intravenous infusion, daily × 5; or a 30-minute loading infusion followed by a 4-hour maintenance infusion, weekly × 2. The alvocidib dose was escalated using a standard 3+3 design. Twenty-eight patients were enrolled and treated. The alvocidib MTD was 20 mg/m(2) (30-minute loading infusion) followed by 20 mg/m(2) (4-hour maintenance infusion) on days one and eight, in combination with vorinostat. The most frequently encountered toxicities were cytopenias, fatigue, hyperglycemia, hypokalemia, hypophosphatemia, and QT prolongation. Dose-limiting toxicities (DLT) were cardiac arrhythmia-atrial fibrillation and QT prolongation. No objective responses were achieved although 13 of 26 evaluable patients exhibited stable disease. Alvocidib seemed to alter vorinostat pharmacokinetics, whereas alvocidib pharmacokinetics were unaffected by vorinostat. Ex vivo exposure of leukemia cells to plasma obtained from patients after alvocidib treatment blocked vorinostat-mediated p21(CIP1) induction and downregulated Mcl-1 and p-RNA Pol II for some specimens, although parallel in vivo bone marrow responses were infrequent. Alvocidib combined with vorinostat is well tolerated. Although disease stabilization occurred in some heavily pretreated patients, objective responses were not obtained with these schedules. ©2013 AACR.

  1. Radiation dose and relapse are predictors for development of second malignant solid tumors after cancer in childhood and adolescence: A population-based case-control study in the five Nordic countries

    International Nuclear Information System (INIS)

    Svahn-Tapper, Gudrun; Garwicz, Stanislaw; Anderson, Harald

    2006-01-01

    The aim of the study was to assess the risk with radiation therapy and chemotherapy of the first cancer in childhood and adolescence for the development of a second malignant solid tumor (SMST). Also, the role of relapse of the primary tumor was studied. It is a nested case-control study within a Nordic cohort of patients less than 20 years of age at first diagnosis 1960-1987. SMSTs were diagnosed in 1960-1991. There were 196 cases and 567 controls. The risk was increased only for radiotherapy given more than five years before the development of the SMST. A significantly increased relative risk of 1.8 was found already at doses below 1 Gy. The risk increased rapidly up to a maximum of 18.3 for doses above 30 Gy. Chemotherapy alone did not increase the risk to develop an SMST. However, in combination with radiotherapy, chemotherapy showed a significant potentiating effect. Relapse was found to be an independent risk factor for development of an SMST, with a higher relative risk for females than for males

  2. Acute traumatic subdural hematoma in infancy and childhood classification and treatment from CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Mochimatsu, Yasuhiko

    1988-11-01

    Acute traumatic subdural hematoma in infancy and childhood has much difference from that in adult on their symptom, clinical course, and indication of surgical treatment. The aim of this study is to examine their clinical course and CT findings just after the injury and to evaluate the treatment modality for types of complex this disease. As the result of these examination, SDH patients are divided into five categories in account of their CT findings, especially according to the relationship between the hemispheric swelling and the amount of SDH. Simple SDH type shows classical clinical course and surgical treatment are frequently essential in rapidly progressive cases. Isodensity hemispheric swelling (IHS) type is more frequently seen in CT findings which shows thin SDH and prominent brain swelling. This IHS (a subtype of diffuse brain injury) type should be recognized for their favourable outcome under conservative treatment. Other three types are; contusion with SDH, acute excerbation of chronic SDH, and battered child. Indication of surgical treatment will be decided considering to the volume of hematomas. (author).

  3. Acute traumatic subdural hematoma in infancy and childhood classification and treatment from CT findings

    International Nuclear Information System (INIS)

    Mochimatsu, Yasuhiko

    1988-01-01

    Acute traumatic subdural hematoma in infancy and childhood has much difference from that in adult on their symptom, clinical course, and indication of surgical treatment. The aim of this study is to examine their clinical course and CT findings just after the injury and to evaluate the treatment modality for types of complex this disease. As the result of these examination, SDH patients are divided into five categories in account of their CT findings, especially according to the relationship between the hemispheric swelling and the amount of SDH. Simple SDH type shows classical clinical course and surgical treatment are frequently essential in rapidly progressive cases. Isodensity hemispheric swelling (IHS) type is more frequently seen in CT findings which shows thin SDH and prominent brain swelling. This IHS (a subtype of diffuse brain injury) type should be recognized for their favourable outcome under conservative treatment. Other three types are; contusion with SDH, acute excerbation of chronic SDH, and battered child. Indication of surgical treatment will be decided considering to the volume of hematomas. (author)

  4. [Spontaneous bile duct perforation: a rare cause of acute abdominal pain during childhood].

    Science.gov (United States)

    Ozdemir, Tunç; Akgül, Ahsen Karagözlü; Arpaz, Yağmur; Arikan, Ahmet

    2008-07-01

    Spontaneous perforation of the bile duct (SPBD) is a rare cause of acute abdominal pain during childhood. Pancreatico-biliary malfunction has been postulated to contribute to its etiology. Factors related to diagnosis and treatment and difference from the other common causes of acute abdominal pain are emphasized. Five patients (3 boys, 2 girls, mean age 4.6) were admitted with peritonitis and operated with initial diagnosis of perforated appendicitis. During laparotomy, SPBD was detected. Presentation, laboratory findings and operative technique of the patients were evaluated retrospectively. Common complaints were abdominal pain and bilious vomiting. Abdominal distention was present in all patients. Leukocytosis and mild hyperbilirubinemia were detected in 5, elevated serum transaminase levels in 4, hyperglycemia in 1 and constipation in 1 patient(s). Abdominal ultrasonography showed a large amount of free fluid. During laparotomy, sterile bile peritonitis was detected initially. After exploration, SPBD was seen. T-tube drainage of the bile duct was carried out. Patients were discharged after removal of the T-tubes. Pancreatico-biliary malfunction was detected in 4 of 5 patients. In patients with generalized peritonitis, elevated transaminase levels and hyperbilirubinemia, SPBD must be considered. Even though the T-tube drainage is the treatment of choice, Roux-en-Y hepatico-portoenterostomy may be mandatory in certain patients.

  5. 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.

  6. Gender differences in alcohol and substance use relapse.

    Science.gov (United States)

    Walitzer, Kimberly S; Dearing, Ronda L

    2006-03-01

    This review explores gender differences in relapse and characteristics of relapse events in alcohol and substance use. For alcohol, relapse rates were similar across gender. Although negative mood, childhood sexual abuse, alcohol-related self-efficacy, and poorer coping strategies predicted alcohol relapse, gender did not moderate these effects. Gender did moderate the association between marriage and alcohol relapse. For women, marriage and marital stress were risk factors for alcohol relapse; among men, marriage lowered relapse risk. This gender difference in the role of marriage in relapse may be a result of partner differences in problem drinking. Alcoholic women are more likely to be married to heavy drinking partners than are alcoholic men; thus, alcoholic women may be put at risk of relapse by marriage and alcoholic men may be protected by marriage. There are fewer studies documenting gender differences in substance abuse relapse so conclusions are limited and tentative. In contrast to the lack of gender differences in alcohol relapse rates, women appear less likely to experience relapse to substance use, relative to men. Women relapsing to substance use appear to be more sensitive to negative affect and interpersonal problems. Men, in contrast, may be more likely to have positive experiences prior to relapse.

  7. Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2018-02-16

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  8. 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

  9. 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...

  10. Brain Activity Associated With Attention Deficits Following Chemotherapy for Childhood Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Fellah, Slim; Cheung, Yin T; Scoggins, Matthew A; Zou, Ping; Sabin, Noah D; Pui, Ching-Hon; Robison, Leslie L; Hudson, Melissa M; Ogg, Robert J; Krull, Kevin R

    2018-05-21

    The impact of contemporary chemotherapy treatment for childhood acute lymphoblastic leukemia on central nervous system activity is not fully appreciated. Neurocognitive testing and functional magnetic resonance imaging (fMRI) were obtained in 165 survivors five or more years postdiagnosis (average age = 14.4 years, 7.7 years from diagnosis, 51.5% males). Chemotherapy exposure was measured as serum concentration of methotrexate following high-dose intravenous injection. Neurocognitive testing included measures of attention and executive function. fMRI was obtained during completion of two tasks, the continuous performance task (CPT) and the attention network task (ANT). Image analysis was performed using Statistical Parametric Mapping software, with contrasts targeting sustained attention, alerting, orienting, and conflict. All statistical tests were two-sided. Compared with population norms, survivors demonstrated impairment on number-letter switching (P < .001, a measure of cognitive flexibility), which was associated with treatment intensity (P = .048). Task performance during fMRI was associated with neurocognitive dysfunction across multiple tasks. Regional brain activation was lower in survivors diagnosed at younger ages for the CPT (bilateral parietal and temporal lobes) and the ANT (left parietal and right hippocampus). With higher serum methotrexate exposure, CPT activation decreased in the right temporal and bilateral frontal and parietal lobes, but ANT alerting activation increased in the ventral frontal, insula, caudate, and anterior cingulate. Brain activation during attention and executive function tasks was associated with serum methotrexate exposure and age at diagnosis. These findings provide evidence for compromised and compensatory changes in regional brain function that may help clarify the neural substrates of cognitive deficits in acute lymphoblastic leukemia survivors.

  11. Comparison of survival outcome between donor types or stem cell sources for childhood acute myeloid leukemia after allogenic hematopoietic stem cell transplantation: A multicenter retrospective study of Study Alliance of Yeungnam Pediatric Hematology-oncology.

    Science.gov (United States)

    Shim, Ye Jee; Lee, Jae Min; Kim, Heung Sik; Jung, Nani; Lim, Young Tak; Yang, Eu Jeen; Hah, Jeong Ok; Lee, Young-Ho; Chueh, Hee Won; Lim, Jae Young; Park, Eun Sil; Park, Jeong A; Park, Ji Kyoung; Park, Sang Kyu

    2018-06-19

    We compared transplant outcomes between donor types and stem cell sources for childhood acute myeloid leukemia (AML). The medical records of children with AML in the Yeungnam region of Korea from January 2000 to June 2017 were reviewed. In all, 76 children with AML (male-to-female ratio = 46:30) received allogenic hematopoietic stem cell transplantation (allo-HSCT). In total, 29 patients received HSCT from either a matched-related donor or a mismatched-related donor, 32 patients received an unrelated donor, and 15 patients received umbilical cord blood. In term of stem cell sources, bone marrow was used in 15 patients and peripheral blood in 46 patients. For all HSCT cases, the 5-year overall survival (OS) was 73.1% (95% CI: 62.7-83.5) and the 5-year event-free survival (EFS) was 66.1% (95% CI: 54.5-77.7). There was no statistical difference in 5-year OS according to the donor types or stem cell sources (P = .869 and P = .911). There was no statistical difference in 5-year EFS between donor types or stem cell sources (P = .526 and P = .478). For all HSCT cases, the 5-year relapse rate was 16.1% (95% CI: 7.3-24.9) and the 5-year non-relapse mortality (NRM) was 13.3% (95% CI: 5.1-21.5). There was no statistical difference in the 5-year relapse rate according to the donor types or stem cell sources (P = .971 and P = .965). There was no statistical difference in the 5-year NRM between donor types or stem cell sources (P = .461 and P = .470). © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients.

    Science.gov (United States)

    Pan, J; Yang, J F; Deng, B P; Zhao, X J; Zhang, X; Lin, Y H; Wu, Y N; Deng, Z L; Zhang, Y L; Liu, S H; Wu, T; Lu, P H; Lu, D P; Chang, A H; Tong, C R

    2017-12-01

    Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD + ) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 × 10 5 /kg and were eventually settled at 1 × 10 5 /kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD + patients achieved MRD - . All of the most recent 20 patients achieved CR/CRi. Most cases only experienced mild to moderate CRS. 8/51 cases had seizures that were relieved by early intervention. Twenty three of twenty seven CR/CRi patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HCT) remained in MRD - with a median follow-up time of 206 (45-427) days, whereas 9 of 18 CR/CRi patients without allo-HCT relapsed. Our results indicate that a low CAR-T-cell dosage of 1 × 10 5 /kg, is effective and safe for treating refractory or relapsed B-ALL, and subsequent allo-HCT could further reduce the relapse rate.

  13. Factors associated with IQ scores in long-term survivors of childhood acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Robison, L.L.; Nesbit, M.E. Jr.; Sather, H.N.; Meadows, A.T.; Ortega, J.A.; Hammond, G.D.

    1984-01-01

    To identify factors which might be associated with intellectual function following treatment for childhood acute lymphoblastic leukemia, 50 long-term survivors were studied using the Wechsler Intelligence Scale for Children-Revised. All patients were diagnosed between 1972 and 1974 and were treated on a single clinical trial protocol with identical induction and maintenance chemotherapy plus central nervous system prophylaxis that included cranial radiation. The mean full scale IQ score for the group was 95 (SEM 2.0), with mean verbal IQ of 94.4 and mean performance IQ of 96.9. Factors which were found to be closely associated with a lower IQ score included female sex (in both verbal IQ and full-scale IQ), longer duration of chemotherapy (in performance IQ), and younger age at the time of radiation (in both verbal IQ and full-scale IQ). The age at the time of radiation was found to be significantly correlated with discrepancy between verbal and performance IQ, with younger age being associated with verbal IQ scores higher than performance IQ scores. When analyses were performed within specific subgroups of patients defined by sex and age at the time of radiation, dose of cranial radiation, concomitant intrathecal methotrexate therapy, and duration of therapy were all found to be correlated with a lower level of intellectual function. These preliminary findings provide direction for future studies to help identify high-risk patients

  14. Educational late effects in long-term survivors of childhood acute lymphocytic leukemia.

    Science.gov (United States)

    Peckham, V C; Meadows, A T; Bartel, N; Marrero, O

    1988-01-01

    Records of levels of school achievement in long-term survivors of childhood acute lymphocytic leukemia were obtained for 23 children who had received 2,400-rad cranial irradiation and intrathecal methotrexate and standard chemotherapeutic agents 8 to 10 years previously. The children had been evaluated with standardized tests of intelligence at the time of diagnosis and periodically thereafter. Declines in IQ and cognitive dysfunctions have been previously described. School placements, educational histories, attendance records, learning strengths and weaknesses, social/emotional adjustments, and grade level achievements in reading and mathematics as measured by standardized achievement tests are reported here. Children achieved less than the expected levels in both reading and mathematics given both pretreatment and most recent IQ scores. Neither sex nor initial IQ were related to achievement scores. Children experienced difficulty with attention/concentration, memory, sequencing, and comprehension when performing school tasks. Individual children showed different degrees of dysfunction, but results of this study suggest that there are patterns of specific learning disabilities rather than global retardation. A small number of children achieved greater than expected levels, indicating that individualized instruction, tutoring, and parental support may reduce some learning deficits. Early educational intervention is recommended for similarly treated patients.

  15. Childhood acute disseminated encephalomyelitis: the role of brain and spinal cord MRI

    International Nuclear Information System (INIS)

    Khong, Pek-Lan; Cheng, Pui-Wai; Chan, Fu-Luk; Ho, Hok-Kung; Wong, Virginia C.N.; Goh, Winnie

    2002-01-01

    Background. It is recognised that the clinical and radiological spectrum of childhood acute disseminated encephalomyelitis (ADEM) is wide. Objective. To determine whether initial MRI features are predictive of clinical outcome and to determine the role of MRI in the management of ADEM. Materials and methods. The MRI scans of ten consecutive children (eight boys, two girls), clinically and radiologically diagnosed to have ADEM, were retrospectively reviewed. Follow-up MRI was available for eight patients. Results. Lesions ranged from small and punctate (<1 cm) to moderate sized and confluent (4-5 cm) to diffuse and extensive. Spinal cord lesions, seen in five of seven children, were contiguous or segmental. Seven children (70%) made good clinical recovery while three children (30%) remained severely handicapped. There was no correlation between the site, extent and pattern of involvement and clinical outcome. However, the evolution of MRI findings on follow-up correlated well with the subsequent clinical course and outcome. Conclusions. Although the extent and site of lesions on initial MRI scans are not predictive of clinical outcome, early MRI of the brain and spine is useful in aiding clinical diagnosis, and subsequent follow-up MRI is helpful in monitoring disease progression. (orig.)

  16. A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia.

    Science.gov (United States)

    Vormoor, B; Veal, G J; Griffin, M J; Boddy, A V; Irving, J; Minto, L; Case, M; Banerji, U; Swales, K E; Tall, J R; Moore, A S; Toguchi, M; Acton, G; Dyer, K; Schwab, C; Harrison, C J; Grainger, J D; Lancaster, D; Kearns, P; Hargrave, D; Vormoor, J

    2017-06-01

    Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies. © 2016 Wiley Periodicals, Inc.

  17. Dose study of the multikinase inhibitor, LY2457546, in patients with relapsed acute myeloid leukemia to assess safety, pharmacokinetics, and pharmacodynamics

    Directory of Open Access Journals (Sweden)

    Wacheck V

    2011-05-01

    Full Text Available Volker Wacheck1, Michael Lahn2, Gemma Dickinson3, Wolfgang Füreder4, Renata Meyer4, Susanne Herndlhofer4, Thorsten Füreder1, Georg Dorfner5, Sada Pillay2, Valérie André6, Timothy P Burkholder7, Jacqueline K Akunda8, Leann Flye-Blakemore9, Dirk Van Bockstaele9, Richard F Schlenk10, Wolfgang R Sperr4, Peter Valent4,111Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria; 2Early Oncology Clinical Investigation, Eli Lilly and Company, Indianapolis, IN, USA; 3Department of Pharmacokinetics, Eli Lilly and Company, Erl Wood Research Centre, Windlesham, Surrey, UK; 4Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria; 5Eli Lilly GesmbH, Medical Department, Vienna, Austria; 6Department of Statistics, Eli Lilly and Company, Erl Wood Research Centre, Surrey, UK; 7Discovery Chemistry Research and Technology, Eli Lilly and Company, Indianapolis, IN, USA; 8Nonclinical Toxicology, Eli Lilly and Company, Indianapolis, IN, USA; 9Flow Cytometry and Cell Analysis, Esoterix Clinical Trials Services, Mechelen, Belgium; 10Universitätsklinikum Ulm, Klinik für Innere Medizin III, Ulm, Germany; 11Ludwig Boltzmann Cluster Oncology, Vienna, AustriaBackground: Acute myeloid leukemia (AML is a life-threatening malignancy with limited treatment options in chemotherapy-refractory patients. A first-in-human dose study was designed to investigate a safe and biologically effective dose range for LY2457546, a novel multikinase inhibitor, in patients with relapsed AML.Methods: In this nonrandomized, open-label, dose escalation Phase I study, LY2457546 was administered orally once a day. Safety, pharmacokinetics, changes in phosphorylation of target kinases in AML blasts, and risk of drug–drug interactions (DDI were assessed.Results: Five patients were treated at the starting and predicted minimal biologically effective dose of 50 mg

  18. Childhood pre-B cell acute lymphoblastic leukemia with translocation t(1;19)(q21.1;p13.3) and two additional chromosomal aberrations involving chromosomes 1, 6, and 13: a case report.

    Science.gov (United States)

    Wafa, Abdulsamad; As'sad, Manar; Liehr, Thomas; Aljapawe, Abdulmunim; Al Achkar, Walid

    2017-04-07

    The translocation t(1;19)(q23;p13), which results in the TCF3-PBX1 chimeric gene, is one of the most frequent rearrangements observed in B cell acute lymphoblastic leukemia. It appears in both adult and pediatric patients with B cell acute lymphoblastic leukemia at an overall frequency of 3 to 5%. Most cases of pre-B cell acute lymphoblastic leukemia carrying the translocation t(1;19) have a typical immunophenotype with homogeneous expression of CD19, CD10, CD9, complete absence of CD34, and at least diminished CD20. Moreover, the translocation t(1;19) correlates with known clinical high risk factors, such as elevated white blood cell count, high serum lactate dehydrogenase levels, and central nervous system involvement; early reports indicated that patients with translocation t(1;19) had a poor outcome under standard treatment. We report the case of a 15-year-old Syrian boy with pre-B cell acute lymphoblastic leukemia with abnormal karyotype with a der(19)t(1;19)(q21.1;p13.3) and two yet unreported chromosomal aberrations: an interstitial deletion 6q12 to 6q26 and a der(13)t(1;13)(q21.1;p13). According to the literature, cases who are translocation t(1;19)-positive have a significantly higher incidence of central nervous system relapse than patients with acute lymphoblastic leukemia without the translocation. Of interest, central nervous system involvement was also seen in our patient. To the best of our knowledge, this is the first case of childhood pre-B cell acute lymphoblastic leukemia with an unbalanced translocation t(1;19) with two additional chromosomal aberrations, del(6)(q12q26) and t(1;13)(q21.3;p13), which seem to be recurrent and could influence clinical outcome. Also the present case confirms the impact of the translocation t(1;19) on central nervous system relapse, which should be studied for underlying mechanisms in future.

  19. When can real-time quantitative RT-PCR effectively define molecular relapse in acute promyelocytic leukemia patients? (Results of the French Belgian Swiss APL Group).

    Science.gov (United States)

    Cassinat, Bruno; de Botton, Stéphane; Kelaidi, Charikleia; Ades, Lionel; Zassadowski, Fabien; Guillemot, Isabelle; Schlageter, Marie-Helene; Raffoux, Emmanuel; Harousseau, Jean-Luc; Legrand, Olivier; Escoffre-Barbe, Martine; Reman, Oumedaly; Gardembas, Martine; Himberlin, Chantal; Cahn, Jean Yves; Guyotat, Denis; Bouscary, Didier; Parry, Anne; Rousselot, Philippe; Baruchel, Andre; Dombret, Hervé; Chevret, Sylvie; Fenaux, Pierre; Chomienne, Christine

    2009-09-01

    10-20% of APL patients relapse and the challenge remains to early identify these patients to improve survival rate. We report PML-RARalpha transcript detection by RQ-PCR in 260 consecutive APL patients (n = 970 samples). 223 patients with samples of sufficient RNA quality to demonstrate they reached molecular remission were monitored for MRD. During follow-up, 38 of these patients were tested positive for PML-RARalpha mRNA. 13 out of the 38 patients (34%) effectively developed hematological relapse. In the first positive sample, specific PML-RARalpha NCN thresholds over which, or under which, patients could effectively be predicted to relapse or not, were identified and subsequently validated in a second cohort.

  20. Daunorubicin, Cytarabine, and Cladribine Regimen Plus Radiotherapy and Donor Lymphocyte Infusion for Extramedullary Relapse of Acute Myeloid Leukemia after Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Marco Sanna

    2013-01-01

    Full Text Available Myeloid sarcoma is a rare tumor consisting of myeloid blasts that involve anatomic sites outside the bone marrow. Fatal prognosis is inevitable in patients with extramedullary relapse after hematopoietic stem cell transplantation (HSCT, and no standard treatments are available yet. We report the first case of extramedullary relapse after HSCT treated with a combination of daunorubicin, cytarabine, and cladribine (DAC regimen plus radiotherapy and donor lymphocyte infusion (DLI. This treatment induced a new and durable remission in our patient. The favorable toxicity profile and the reduced cost make this combination worthy of further investigations.

  1. 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.

  2. Low-dose total body irradiation and G-CSF without hematopoietic stem cell support in the treatment of relapsed or refractory acute myelogenous leukemia (AML), or AML in second or subsequent remission

    International Nuclear Information System (INIS)

    Shulman, Lawrence N.; Tarbell, Nancy J.; Storen, Elizabeth; Marcus, Karen; Mauch, Peter M.

    1998-01-01

    Purpose: Patients with relapsed acute myelogenous leukemia (AML), who are not eligible for bone marrow transplantation, have a poor prognosis when treated with chemotherapy alone. Total body irradiation (TBI) is an effective modality against AML when used in doses of 1000-1400 cGy with hematopoietic stem cell support. We undertook a phase I study of TBI with granulocyte-colony-stimulating factor (G-CSF) support, without stem cell support in patients with AML either in relapse or second or subsequent remission. Methods and Materials: Patients with relapsed AML, or AML in second or subsequent remission were treated in a phase I study of TBI followed by G-CSF. The first dose level was 200 cGy. After the initial cohort of patients it was clear that patients with overt leukemia did not benefit from this treatment, and subsequent patients were required to be in remission at the time of TBI. Results: Eleven patients were treated, 4 in overt relapse, and 7 in remission. 200 cGy was used in all, and dose escalation was not possible due to prolonged thrombocytopenia in all patients but one. Neutrophil recovery was adequate in those patients who remained in remission after TBI. Patients with overt leukemia had transient reduction in blast counts, but rapid recurrence of their leukemia. Patients treated in remission had short remissions, with the exception of one patient who is in remission 32 months after treatment. Conclusion: There is some antileukemic effect of TBI even at 200 cGy, though this dose appears to be too low to help a significant number of patients. If TBI is to be escalated without stem cell support, then a thrombopoietic agent will need to be used

  3. A lifetime approach to major depressive disorder: The contributions of psychological interventions in preventing relapse and recurrence.

    Science.gov (United States)

    Bockting, Claudi L; Hollon, Steven D; Jarrett, Robin B; Kuyken, Willem; Dobson, Keith

    2015-11-01

    Major depressive disorder (MDD) is highly disabling and typically runs a recurrent course. Knowledge about prevention of relapse and recurrence is crucial to the long-term welfare of people who suffer from this disorder. This article provides an overview of the current evidence for the prevention of relapse and recurrence using psychological interventions. We first describe a conceptual framework to preventive interventions based on: acute treatment; continuation treatment, or; prevention strategies for patients in remission. In brief, cognitive-behavioral interventions, delivered during the acute phase, appear to have an enduring effect that protects patients against relapse and perhaps others from recurrence following treatment termination. Similarly, continuation treatment with either cognitive therapy or perhaps interpersonal psychotherapy appears to reduce risk for relapse and maintenance treatment appears to reduce risk for recurrence. Preventive relapse strategies like preventive cognitive therapy or mindfulness based cognitive therapy (MBCT) applied to patients in remission protects against subsequent relapse and perhaps recurrence. There is some preliminary evidence of specific mediation via changing the content or the process of cognition. Continuation CT and preventive interventions started after remission (CBT, MBCT) seem to have the largest differential effects for individuals that need them the most. Those who have the greatest risk for relapse and recurrence including patients with unstable remission, more previous episodes, potentially childhood trauma, early age of onset. These prescriptive indications, if confirmed in future research, may point the way to personalizing prevention strategies. Doing so, may maximize the efficiency with which they are applied and have the potential to target the mechanisms that appear to underlie these effects. This may help make this prevention strategies more efficacious. Copyright © 2015 Elsevier Ltd. All rights

  4. Relapses in Multiple Sclerosis: Definition, Pathophysiology, Features, Imitators, and Treatment

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    Serhan Sevim

    2016-09-01

    Full Text Available Relapse in multiple sclerosis (MS is defined as a neurologic deficit associated with an acute inflammatory demyelinating event that lasts at least 24 hours in the absence of fever and infection. Myelinoclasis and axonal transection occur in relapses. Diagnosis, prognosis, treatment, and many other features of the disease are directly related to the relapses. MS starts as the relapsing-remitting (RRMS form in 85% of patients. A large number of relapses in the first years, polysymptomatic relapses, and pyramidal system, brain stem, and spinal cord involvement are signs of a poor outcome. The average frequency of relapses is approximately one per year during the first years of RRMS. The frequency of relapses increases during systemic infections, psychological stress, and in the postpartum first 3 months. Seventy-five percent of relapses are monosymptomatic. Pseudo-relapses and paroxysmal symptoms are distinguished from relapses by their sudden onset, sudden termination, and shorter duration. Contrast enhancement is valuable in imaging, but undetectable in most relapses. The regression in the first few weeks of relapses is explained by reduction of the edema, and by remyelination in the following months. Relapses and their features are also among the main determinants of treatment. High-dose methylprednisolone and early treatment with adrenocorticotropic hormone reduce post-relapse disability and shorten the duration of relapses. Plasmapheresis is a good option for patients who do not respond to steroid treatment. Identification of relapses by patients and physicians, distinguishing them from imitators, proper evaluation, treatment when necessary, and monitoring the results are of great importance for patients with MS. The educational levels of patients and physicians regarding these parameters should be increased. Well-designed studies that evaluate the long-term effect of relapse treatment on disability are needed.

  5. Tobacco smoke and risk of childhood acute non-lymphocytic leukemia: findings from the SETIL study.

    Directory of Open Access Journals (Sweden)

    Stefano Mattioli

    Full Text Available Parental smoking and exposure of the mother or the child to environmental tobacco smoke (ETS as risk factors for Acute non-Lymphocytic Leukemia (AnLL were investigated.Incident cases of childhood AnLL were enrolled in 14 Italian Regions during 1998-2001. We estimated odds ratios (OR and 95% confidence intervals (95%CI conducting logistic regression models including 82 cases of AnLL and 1,044 controls. Inverse probability weighting was applied adjusting for: age; sex; provenience; birth order; birth weight; breastfeeding; parental educational level age, birth year, and occupational exposure to benzene.Paternal smoke in the conception period was associated with AnLL (OR for ≥ 11 cigarettes/day  = 1.79, 95% CI 1.01-3.15; P trend 0.05. An apparent effect modification by maternal age was identified: only children of mothers aged below 30 presented increased risks. We found weak statistical evidence of an association of AnLL with maternal exposure to ETS (OR for exposure>3 hours/day  = 1.85, 95%CI 0.97-3.52; P trend 0.07. No association was observed between AnLL and either maternal smoking during pregnancy or child exposure to ETS.This study is consistent with the hypothesis that paternal smoke is associated with AnLL. We observed statistical evidence of an association between maternal exposure to ETS and AnLL, but believe bias might have inflated our estimates.

  6. Tobacco Smoke and Risk of Childhood Acute Non-Lymphocytic Leukemia: Findings from the SETIL Study

    Science.gov (United States)

    Mattioli, Stefano; Farioli, Andrea; Legittimo, Patrizia; Miligi, Lucia; Benvenuti, Alessandra; Ranucci, Alessandra; Salvan, Alberto; Rondelli, Roberto; Magnani, Corrado

    2014-01-01

    Background Parental smoking and exposure of the mother or the child to environmental tobacco smoke (ETS) as risk factors for Acute non-Lymphocytic Leukemia (AnLL) were investigated. Methods Incident cases of childhood AnLL were enrolled in 14 Italian Regions during 1998–2001. We estimated odds ratios (OR) and 95% confidence intervals (95%CI) conducting logistic regression models including 82 cases of AnLL and 1,044 controls. Inverse probability weighting was applied adjusting for: age; sex; provenience; birth order; birth weight; breastfeeding; parental educational level age, birth year, and occupational exposure to benzene. Results Paternal smoke in the conception period was associated with AnLL (OR for ≥11 cigarettes/day  = 1.79, 95% CI 1.01–3.15; P trend 0.05). An apparent effect modification by maternal age was identified: only children of mothers aged below 30 presented increased risks. We found weak statistical evidence of an association of AnLL with maternal exposure to ETS (OR for exposure>3 hours/day  = 1.85, 95%CI 0.97–3.52; P trend 0.07). No association was observed between AnLL and either maternal smoking during pregnancy or child exposure to ETS. Conclusions This study is consistent with the hypothesis that paternal smoke is associated with AnLL. We observed statistical evidence of an association between maternal exposure to ETS and AnLL, but believe bias might have inflated our estimates. PMID:25401754

  7. Thiopurine methyltransferase genotype-phenotype discordance and thiopurine active metabolite formation in childhood acute lymphoblastic leukaemia.

    Science.gov (United States)

    Lennard, Lynne; Cartwright, Cher Suzanne; Wade, Rachel; Richards, Susan M; Vora, Ajay

    2013-07-01

    In children with acute lymphoblastic leukaemia (ALL) bone marrow activity can influence red blood cell (RBC) kinetics, the surrogate tissue for thiopurine methyltransferase (TPMT) measurements. The aim of this study was to investigate TPMT phenotype-genotype concordance in ALL, and the influence of TPMT on thiopurine metabolite formation. We measured TPMT (activity, as units ml(-1) packed RBCs and genotype) at diagnosis (n = 1150) and TPMT and thioguanine nucleotide (TGN) and methylmercaptopurine nucleotide (MeMPN) metabolites (pmol/8 × 10(8) RBCs) during chemotherapy (n = 1131) in children randomized to thioguanine or mercaptopurine on the United Kingdom trial ALL97. Median TPMT activity at diagnosis (8.5 units) was significantly lower than during chemotherapy (13.8 units, median difference 5.1 units, 95% confidence interval (CI) 4.8, 5.4, P mercaptopurine, median TGNs were higher in TPMT heterozygous genotype (754 pmol) than wild-type (360 pmol) patients (median difference 406 pmol, 95% CI 332, 478, P products of the TPMT reaction, were higher in wild-type (10 650 pmol) than heterozygous patients (3868 pmol) (P < 0.0001). In TPMT intermediate activity patients with a wild-type genotype, TGN (median 366 pmol) and MeMPN (median 8590 pmol) concentrations were similar to those in wild-type, high activity patients. In childhood ALL, TPMT activity should not be used to predict heterozygosity particularly in blood samples obtained at disease diagnosis. Genotype is a better predictor of TGN accumulation during chemotherapy. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  8. Thiopurine methyltransferase genotype–phenotype discordance and thiopurine active metabolite formation in childhood acute lymphoblastic leukaemia

    Science.gov (United States)

    Lennard, Lynne; Cartwright, Cher Suzanne; Wade, Rachel; Richards, Susan M; Vora, Ajay

    2013-01-01

    Aims In children with acute lymphoblastic leukaemia (ALL) bone marrow activity can influence red blood cell (RBC) kinetics, the surrogate tissue for thiopurine methyltransferase (TPMT) measurements. The aim of this study was to investigate TPMT phenotype–genotype concordance in ALL, and the influence of TPMT on thiopurine metabolite formation. Methods We measured TPMT (activity, as units ml−1 packed RBCs and genotype) at diagnosis (n = 1150) and TPMT and thioguanine nucleotide (TGN) and methylmercaptopurine nucleotide (MeMPN) metabolites (pmol/8 × 108 RBCs) during chemotherapy (n = 1131) in children randomized to thioguanine or mercaptopurine on the United Kingdom trial ALL97. Results Median TPMT activity at diagnosis (8.5 units) was significantly lower than during chemotherapy (13.8 units, median difference 5.1 units, 95% confidence interval (CI) 4.8, 5.4, P mercaptopurine, median TGNs were higher in TPMT heterozygous genotype (754 pmol) than wild-type (360 pmol) patients (median difference 406 pmol, 95% CI 332, 478, P products of the TPMT reaction, were higher in wild-type (10 650 pmol) than heterozygous patients (3868 pmol) (P < 0.0001). In TPMT intermediate activity patients with a wild-type genotype, TGN (median 366 pmol) and MeMPN (median 8590 pmol) concentrations were similar to those in wild-type, high activity patients. Conclusions In childhood ALL, TPMT activity should not be used to predict heterozygosity particularly in blood samples obtained at disease diagnosis. Genotype is a better predictor of TGN accumulation during chemotherapy. PMID:23252716

  9. Long-term sequelae after chemotherapy and radiotherapy for childhood acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Reiter, G.E.P.

    1994-12-01

    Background: Effective forms of treatment for acute lymphoblastic leukemia (ALL) in childhood now result in survival rates of more than 70%. With improving cure rates increasing interest has been focused on adverse late effects caused by chemotherapy and cranial irradiation. Methods: We investigated 40 survivors, 22 males and 18 females with an average age of 15.8 years (6.6 to 28.1), all treated at the Children's Hospital of Innsbruck, Austria, after a follow-up of 9.2 years (4.6 - 20) on average in continuous complete remission. Our evaluation included cardiac status, growth, endocrinological function and a wide variety of other clinical and laboratory investigations. To identify cardiac dysfunction due to anthracyclines we performed Dobutamine-Stress-Echocardiography (DSE) using a graded dosage regimen (1.0, 2.5 and 5.0 μg/kg/min). We compared the DSE data with those obtained from 17 age-matched control subjects. Results: Conventional echocardiography revealed only 4 patients (11.4%) with abnormalities of left ventricular contractility (measured as left ventricular shortening fraction). In contrast DSE detected a 3-fold higher percentage of patients with cardiac dysfunction. There was no correlation between total cumulative anthracycline dose, age at time of diagnosis and length of follow-up with incidence of abnormalities. Primary hypothyroidism in 4 patients (10%) and a permanent linear growth retardation in 5 patients (12%, all of which had been irradiated) were the only endocrinological problems detected. No survivor showed hemato-immunological disturbances. Remarkably, transfusion- associated sequelae, liver or kidney dysfunction were not found. Conclusion: The high incidence of late cardiac effects requires continued monitoring of patients after ALL treatment. In this respect, DSE revealed to be a sensitive method. (author)

  10. Genetic evaluation of childhood acute lymphoblastic leukemia in Iraq using FTA cards.

    Science.gov (United States)

    Al-Kzayer, Lika'a Fasih Y; Sakashita, Kazuo; Matsuda, Kazuyuki; Al-Hadad, Salma Abbas; Al-Jadiry, Mazin Faisal; Abed, Wisam Majeed; Abdulkadhim, Jaafar M H; Al-Shujairi, Tariq Abadi; Hasan, Janan Ghalib; Al-Abdullah, Hussam M Salih; Al-Ani, Mouroge H; Saber, Paiman Ali I; Inoshita, Toshi; Kamata, Minoru; Koike, Kenichi

    2012-09-01

    Genetic examination of childhood leukemia has not been available in Iraq. We here report the frequency of TEL-AML1, E2A-PBX1, MLL-AF4, and BCR-ABL chimeric transcripts in 264 Iraqi children newly diagnosed with acute lymphoblastic leukemia (ALL), using FTA cards impregnated with bone marrow aspirate or whole blood. The diagnosis of ALL was made according to standard French-American-British morphologic criteria. Based on the results of storage temperature and duration, most of the FTA samples were preserved at 4°C for up to 6 weeks in five Iraqi hospitals and then transferred to Japan for molecular analysis. Nested reverse transcription-polymerase chain reaction was adopted for the analysis. TEL-AML1 chimeric transcript product was found in 32 (12.1%) of 264 ALL patients. Eleven (4.2%) patients, 4 (1.5%) patients, and 11 (4.2%) patients had E2A-PBX1 mRNA, MLL-AF4 mRNA, and BCR-ABL mRNA, respectively. One patient had both TEL-AML1 and E2A-PBX1 fusion genes. The incidence of TEL-AML1 in Iraqi ALL children appears to be similar to or slightly higher than those of Jordan (12%) and Kuwait (7%). The prevalence and clinical findings of ALL patients with either E2A-PBX1 or BCR-ABL were comparable to the data reported elsewhere. International collaboration via FTA cards may be helpful to improve diagnosis and management of patients with hematological malignancies in low-income and underdeveloped countries. Copyright © 2012 Wiley Periodicals, Inc.

  11. CT studies before and after CNS treatment for acute lymphoblastic leukemia and malignant non-Hodgkin's lymphoma in childhood

    International Nuclear Information System (INIS)

    Kretzschmar, K.; Gutjahr, P.; Kutzner, J.

    1980-01-01

    CT was performed on 72 children with acute lymphoblasitc leukemia or non-Hodgkin's lymphoma. Thirty-two of these patients were investigated prior to CNS radiation and intrathecal methotrexate therapy. Ten of these patients (31%) were known to have hydrocephalic dilatation of the CSF spaces. Clinical data and subsequent observations with analysis of the CT findings show that no difference in the attenuation values of brain tissue occurs in the absence of a CNS relapse. The percentage of abnormal findings before and after therapy remains constant. The adverse late effects described in the CT literature seem principally to be damage diagnosed too late. It is questionable if the CT demonstration of dilated CSF spaces before treatment has a prognostic significance. (orig.)

  12. Expression levels of hsc70 and hsp60 are developmentally regulated during B-cell maturation and not associated to childhood c-ALL at presentation or relapse

    DEFF Research Database (Denmark)

    Wehner, Peder Skov; Nielsen, Bendt; Hokland, Marianne

    2003-01-01

    ) or heat shock protein 60 (hsp60) contribute to B-cell differentiation and leukemogenesis. We compared the expression of these hsps in normal peripheral blood (PB) CD19+ B-cells, in pediatric bone marrow (BM) CD19+ CD10+ B-cell precursors (BCPs) from normal donors, and in BCPs from common acute......Heat shock proteins are potent regulators of apoptosis, and so they may also be involved in normal cellular differentiation and cancerogenesis. We used quantitative two-dimensional gel electrophoresis for determining whether either the constitutive chaperonic heat shock cognate protein 70 (hsc70...

  13. Pharmacogenetics in Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Cheok, Meyling H.; Pottier, Nicolas; Kager, Leo

    2009-01-01

    Progress in the treatment of acute leukemia in children has been remarkable, from a disease being lethal four decades ago to current cure rates exceeding 80%. This exemplary progress is largely due to the optimization of existing treatment modalities rather than the discovery of new antileukemic agents. However, despite these high cure rates, the annual number of children whose leukemia relapses after their initial therapy remains greater than that of new cases of most types of childhood cancers. The aim of pharmacogenetics is to develop strategies to personalize treatment and tailor therapy to individual patients, with the goal of optimizing efficacy and safety through better understanding of human genome variability and its influence on drug response. In this review, we summarize recent pharmacogenomic studies related to the treatment of pediatric acute lymphoblastic leukemia. These studies illustrate the promise of pharmacogenomics to further advance the treatment of human cancers, with childhood leukemia serving as a paradigm. PMID:19100367

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

    Science.gov (United States)

    2018-02-22

    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

  15. Genes commonly deleted in childhood B-cell precursor acute lymphoblastic leukemia: association with cytogenetics and clinical features

    Science.gov (United States)

    Schwab, Claire J.; Chilton, Lucy; Morrison, Heather; Jones, Lisa; Al-Shehhi, Halima; Erhorn, Amy; Russell, Lisa J.; Moorman, Anthony V.; Harrison, Christine J.

    2013-01-01

    In childhood B-cell precursor acute lymphoblastic leukemia, cytogenetics is important in diagnosis and as an indicator of response to therapy, thus playing a key role in risk stratification of patients for treatment. Little is known of the relationship between different cytogenetic subtypes in B-cell precursor acute lymphoblastic leukemia and the recently reported copy number abnormalities affecting significant leukemia associated genes. In a consecutive series of 1427 childhood B-cell precursor acute lymphoblastic leukemia patients, we have determined the incidence and type of copy number abnormalities using multiplex ligation-dependent probe amplification. We have shown strong links between certain deletions and cytogenetic subtypes, including the novel association between RB1 deletions and intrachromosomal amplification of chromosome 21. In this study, we characterized the different copy number abnormalities and show heterogeneity of PAX5 and IKZF1 deletions and the recurrent nature of RB1 deletions. Whole gene losses are often indicative of larger deletions, visible by conventional cytogenetics. An increased number of copy number abnormalities is associated with NCI high risk, specifically deletions of IKZF1 and CDKN2A/B, which occur more frequently among these patients. IKZF1 deletions and rearrangements of CRLF2 among patients with undefined karyotypes may point to the poor risk BCR-ABL1-like group. In conclusion, this study has demonstrated in a large representative cohort of children with B-cell precursor acute lymphoblastic leukemia that the pattern of copy number abnormalities is highly variable according to the primary genetic abnormality. PMID:23508010

  16. Final height and body mass index after treatment for childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Tadej Battelino

    2006-03-01

    Full Text Available Background: Newer and more agressive forms of chemotherapy and newer protocols in the treatment have increased the survival rate of children with malignancies. Improved survival rates in children treated for acute lymphoblastic leukemia have focused attention on late effects including disorders of growth and puberty, and development of overweight or obesity.Methods: The height and weight expressed as body mass index (BMI of 47 patients (29 girls, 18 boys long-term survivors of childhood lymphoblastic leukemia was retrospectively analyzed. Height standard deviation score (HSDS according to Tanner and body mass index standard deviation scores (BMISDS before treatment and at follow-up were calculated. At the time of analysis all patients remained in first remission. Twenty-eight patients had cranial radiation with 12–18 Gy and 15 with 20–30 Gy. Four patients had no radiotherapy. All patients were treated with standard chemotherapy including intrathecal Methotrexat. Mean age (SD at the diagnosis was 5 5/12 (3 2/12 years, range (5/12 – 12 5/12 and at the time of evaluation 17 11/12 (3 9/12 years, range (10 1/12 – 31 6/12.Results: We observed significant decrease in HSDS from diagnosis to the final height in both radiation groups (p < 0.01 but the decrement in final height was similar with both radiation dose regimens. The decrement in final height SDS was greater in patients treated at a younger age (Pearson, p < 0.01. Girls treated with higher radiation dose (20–30 Gy were more severely affected than boys. In both radiation dose treatment groups there was a significant increase in BMISDS between diagnosis and final height (p < 0.0001 with no significant difference between treatment groups. Menarche occurred earlier in girls than normal with no significant difference between both radiation dose regimens.Conclusions: We observed significant deterioration in HSDS and increment in BMISDS regardless to the radiation dose.

  17. Cranial irradiation of leukaemia in childhood

    International Nuclear Information System (INIS)

    Gyenes, Gy.; Sator, G.; Varjas, G.

    1979-01-01

    The fundamental combined cytostatic treatment, initiated immediatly after the diagnosis, of the acute lymphoid leukaemia in the childhood is the method of choice. The haematologic remission, however, does not signify recovery, the starting-place of the relapse is mostly in the central nervous system. Telecobalt irradiation of the neurocranium using the known ray-physical and ray-biological advantages regularly distroys the leukaemia cells hidden in this region. In the paper the experiences gained with the irradiation of 151 children are reported. Further ulterior informations could be obtained by the authors only from 66 patients, out of them meningeosis leukaemia developed in 12%. (author)

  18. Upregulation of microRNA-21 is a poor prognostic marker in patients with childhood B cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Labib, Hany Abedelmalik; Elantouny, Neveen G; Ibrahim, Nevin F; Alnagar, Ahmed A

    2017-08-01

    Many studies have demonstrated that microRNA-21 (miR-21) is an oncogene and is upregulated in tumor tissue. However, its association with B-cell acute lymphoblastic leukemia (B-ALL) remains poorly understood. The expression of miR-21 was detected by real-time quantitative PCR in 75 children with de novo B-ALL as well as in 50 healthy controls. This study was conducted to evaluate the miR-21 as a biomarker for risk assessment, diagnosis and prognosis. Compared with normal controls, miR-21 expression was significantly upregulated in childhood B-ALL patients. Using the receiver operating characteristic curve 3.23 was selected as the cut-off value of miR-21 expression in distinguishing patients from controls. Patients group with High miR-21 expression was significantly associated with those aged 10 years, lower platelets count, more incidence of CNS infiltration and poorer treatment outcome also, they showed a significantly poorer disease-free survival (DFS) and overall survival (OS) compared to those with low miR-21 expression group. Its expression was an independent prognostic marker according to multivariate analysis. This is the first report demonstrating the upregulation of miR-21 in childhood B-ALL, and its association with poor response to induction therapy, shorter DFS and OS. These results suggest that miR-21 upregulation represent an unfavorable prognostic marker in Childhood B-ALL.

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

    Directory of Open Access Journals (Sweden)

    Skegg David CG

    2007-07-01

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

  20. The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse

    DEFF Research Database (Denmark)

    Schmiegelow, K; Donovan, Martin Heyman; Sherson, Maiken Gustafsson

    2010-01-01

    Drug doses, blood levels of drug metabolites and myelotoxicity during 6-mercaptopurine/methotrexate (MTX) maintenance therapy were registered for 59 adolescents (10 years) and 176 non-adolescents (leukemia (ALL) and a white blood cell count (WBC......) diagnosis. Event-free survival was lower for adolescents than non-adolescents (pEFS12y:0.71 vs 0.83, P=0.04). For adolescents staying in remission, the mean WBC during maintenance therapy (mWBC) was related to age (rS=0.36, P=0.02), which became nonsignificant for those who relapsed (r...

  1. Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis

    NARCIS (Netherlands)

    P. Montesinos (Pau); J. Díaz-Mediavilla (Joaquín); G. Debén (Guillermo); V. Prates (Virginia); M. Tormo (Mar); V. Rybio (Vicente); I. Pérez (Inmaculada); I. Fernández (Isolda); M. Viguria (Maricruz); C. Rayón (Chelo); J. de Serna (Javier); J. Esteve (Jordi); J.M. Bergua (Juan Miguel); C. Rivas (Concha); J.D. González (José David); M. González (Marcos); S. Negri (Silvia); S. Brunet (Salut); B. Löwenberg (Bob); M.A. Sanz (Miguel Angel)

    2009-01-01

    textabstractBackground: The prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter. Design and Methods: Between 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic

  2. Mitoxantrone, etoposide and cytarabine following epigenetic priming with decitabine in adults with relapsed/refractory acute myeloid leukemia or other high-grade myeloid neoplasms: a phase 1/2 study.

    Science.gov (United States)

    Halpern, A B; Othus, M; Huebner, E M; Buckley, S A; Pogosova-Agadjanyan, E L; Orlowski, K F; Scott, B L; Becker, P S; Hendrie, P C; Chen, T L; Percival, M-E M; Estey, E H; Stirewalt, D L; Walter, R B

    2017-12-01

    DNA methyltransferase inhibitors sensitize leukemia cells to chemotherapeutics. We therefore conducted a phase 1/2 study of mitoxantrone, etoposide and cytarabine following 'priming' with 5-10 days of decitabine (dec/MEC) in 52 adults (median age 55 (range: 19-72) years) with relapsed/refractory acute myeloid leukemia (AML) or other high-grade myeloid neoplasms. During dose escalation in cohorts of 6-12 patients, all dose levels were well tolerated. As response rates appeared similar with 7 and 10 days of decitabine, a 7-day course was defined as the recommended phase 2 dose (RP2D). Among 46 patients treated at/above the RP2D, 10 (22%) achieved a complete remission (CR), 8 without measurable residual disease; five additional patients achieved CR with incomplete platelet recovery, for an overall response rate of 33%. Seven patients (15%) died within 28 days of treatment initiation. Infection/neutropenic fever, nausea and mucositis were the most common adverse events. While the CR rate compared favorably to a matched historic control population (observed/expected CR ratio=1.77), CR rate and survival were similar to two contemporary salvage regimens used at our institution (G-CLAC (granulocyte colony-stimulating factor (G-CSF); clofarabine; cytarabine) and G-CLAM (G-CSF; cladribine; cytarabine; mitoxantrone)). Thus, while meeting the prespecified efficacy goal, we found no evidence that dec/MEC is substantially better than other cytarabine-based regimens currently used for relapsed/refractory AML.

  3. Childhood Leukemia

    Science.gov (United States)

    ... acute types. Symptoms include Infections Fever Loss of appetite Tiredness Easy bruising or bleeding Swollen lymph nodes Night sweats Shortness of breath Pain in the bones or joints Risk factors for childhood leukemia include having a brother ...

  4. Differences in disease features between childhood-onset and adult-onset systemic lupus erythematosus patients presenting with acute abdominal pain.

    Science.gov (United States)

    Tu, Yu-Ling; Yeh, Kuo-Wei; Chen, Li-Chen; Yao, Tsung-Chieh; Ou, Liang-Shiou; Lee, Wen-I; Huang, Jing-Long

    2011-04-01

    Abdominal pain in systemic lupus erythematosus (SLE) patients has rarely been analyzed in pediatric populations. We planned to investigate the potential differences between childhood-onset and adult-onset SLE patients who were hospitalized because of acute abdominal pain. A retrospective study including 23 childhood-onset SLE patients with 38 admissions and 88 adult-onset SLE patients with 108 admissions from 1999 to 2008 were conducted in our hospital. All of them had the chief complaint of diffuse abdominal pain. The etiologies of acute abdominal pain in adult-onset SLE patients were more diverse than childhood-onset SLE patients. The most common cause of acute abdominal pain in SLE patients was lupus mesenteric vasculitis (LMV) (18.5%), followed by acute gastroenteritis (14.4%), pancreatitis (10.3%), appendicitis (7.5%), and cholecystitis (6.2%). Compared with adults, children were admitted more often due to LMV (31.6% versus 13.9%; P = 0.016), had more frequently recurrent episodes (39.1% versus 14.8%; P = 0.009), and were more often treated with immunosuppressive agents (31.6% versus 7.4%; P abdominal pain should be considered in SLE patients. LMV is the most common cause of acute abdomen in childhood-onset SLE patients with low mortality and morbidity provided by prompt diagnosis and timely administration of high-dose intravenous corticosteroids after excluding real surgical abdomen. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Tiffany-Jane Evans

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

  6. Complications in the central nervous system during chemotherapy for childhood acute lymphoblastic leukemia. JACLS ALL-02 study

    International Nuclear Information System (INIS)

    Umeda, Katsutsugu; Yoshida, Makoto; Suzuki, Nobuhiro

    2007-01-01

    We evaluated central nervous system (CNS) complications treated under the ALL-02 protocol of the Japan Association of Childhood Leukemia Study (JACLS) from April 2002 to March 2005. According to National Cancer Institute (NCI) Toxicity Criteria, 17 events of grade 3 and 4 CNS complications were reported in 15 out of 541 patients. Out of these CNS complications, leukoencephalopathy was seen in 5 patients; seizure in 5; cerebrovascular disease in 3; conscious disturbance in 2; and hypertensive encephalopathy and reversible posterior leukoencephalopathy syndrome in one patient each. The complications were intensively observed during induction therapy and the last of the early phase chemotherapy. The protocol treatment was stopped or modified in most patients after CNS complications. MRI imaging demonstrated no improvement in one patient with leukoencephalopathy who developed an isolated CNS relapse, while other patients were alive and remain in their first complete remission without any neurological sequelae. Further studies will be required to analyze risk factors for CNS complications during chemotherapy not accompanied by irradiation and to establish alternative treatments after the appearance of such CNS complications. (author)

  7. High-resolution Antibody Array Analysis of Childhood Acute Leukemia Cells

    Czech Academy of Sciences Publication Activity Database

    Kanderová, V.; Kuzilkova, D.; Stuchlý, J.; Vašková, M.; Brdička, Tomáš; Fišer, K.; Hrušák, O.; Lund-Johansen, F.; Kalina, T.

    2016-01-01

    Roč. 15, č. 4 (2016), s. 1246-1261 ISSN 1535-9476 R&D Projects: GA MŠk 2B06064 Institutional support: RVO:68378050 Keywords : acute lymphoblastic-leukemia * acute promyelocytic leukemia * cytometric immunobead assay * caspase-dependent cleavage * acute myeloid-leukemia * gene-expression * fusion proteins * flow-cytometry * pcr data * b-cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.540, year: 2016

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

    Science.gov (United States)

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

    2016-10-01

    Survivors of childhood acute lymphoblastic leukaemia (ALL) are at risk for neurocognitive deficits that affect development in adolescence and young adulthood, and influence educational attainment and future independence. We examined a large and diverse cohort of survivors to identify risk predictors and modifiers of these outcomes. In this cohort study, cognitive and behaviour symptoms were assessed via a standardised parent questionnaire for 1560 adolescent survivors of ALL diagnosed between 1970 and 1999. Clinically significant symptoms (≥90th percentile) and learning problems were compared between survivors and a sibling cohort. Multivariable regression models were used to examine associations with demographic and treatment characteristics. Models were adjusted for inverse probability of sampling weights to reflect undersampling of ALL survivors in the expansion cohort. In a subset of survivors with longitudinal data (n=925), we examined associations between adolescent symptoms or problems and adult educational attainment. Compared with siblings, survivors treated with chemotherapy only were more likely to demonstrate headstrong behaviour (155 [19%] of 752 survivors vs 88 [14%] of 610 siblings, p=0·010), inattention-hyperactivity (15 [19%] vs 86 [14%], p4·3 g/m 2 ) conferred increased risk of inattention-hyperactivity (relative risk [RR] 1·53, 95% CI 1·13-2·08). Adolescent survivors with cognitive or behaviour problems and those with learning problems were less likely to graduate from college as young adults than adolescent survivors without cognitive or behaviour problems. Although modern therapy for childhood ALL has eliminated the use of cranial radiation therapy, adolescent survivors treated with chemotherapy only remain at increased risk for cognitive, behaviour, and academic problems that adversely affect adult education outcomes. National Cancer Institute, American Lebanese-Syrian Associated Charities. Copyright © 2016 Elsevier Ltd. All rights

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  10. Cost-Effectiveness of Treatment of Childhood Acute Lymphoblastic Leukemia With Chemotherapy Only: The Influence of New Medication and Diagnostic Technology

    NARCIS (Netherlands)

    van Litsenburg, R.R.L.; Uyl-de Groot, C.A.; Raat, H.; Kaspers, G.J.L.; Gemke, R.J.B.J.

    2011-01-01

    Background: Survival for childhood acute lymphoblastic leukemia (ALL) has reached 80-90%. Future improvement in treatment success will involve new technologies and medication, adding to the pressure on limited financial resources. Therefore a retrospective cost-effectiveness analysis of ALL

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  12. Reduction of adult height in childhood acute lymphoblastic leukemia survivors after prophylactic cranial irradiation

    NARCIS (Netherlands)

    Bongers, MEJ; Francken, AB; Rouwe, C; Kamps, WA; Postma, A

    Background. Impaired linear growth is a well-recognized complication in long-term childhood ALL survivors who received cranial irradiation. However, as many patients achieve a final height between the 5th and the 95th centile, the true incidence of linear growth impairment might be underestimated.

  13. Current status of total body irradiation in conditioning regimen for childhood acute lymphoblastic leukemia. Survey in the Japan Association of Childhood Leukemia Study (JACLS) Group

    International Nuclear Information System (INIS)

    Suzuki, Nobuhiro; Hara, Jun-ichi; Chayama, Kohsuke; Akiyama, Yuichi; Nakahata, Tatsutoshi

    2005-01-01

    We surveyed methods of total body irradiation (TB I) in conditioning regimens of stem cell transplantation (SCT) for children with acute lymphoblastic leukemia (ALL) at participating institutions of the Japan Association of Childhood Leukemia Study (JACLS) ALL-97 protocol. We obtained information about TBI from 25 institutions. Total dose of 12 Gy fractionated by four to six in two to three days for TBI was conducted in 22 of 25 institutions. High-risk patients, such as patients with Philadelphia positive ALL, received over 12 Gy in five institutions. Beam direction and patient's positioning were horizontal and lateral respectively in 15 institutions. Shielding of lung and/or eyes and boost irradiation to central nervous system and/or testis were done in 24 and 11 institutions respectively, but in various ways. We have to keep in mind that a great variety of TBI have been undergone in each institution when we intend to interpret multi-institutional trials of treatment including SCT for patients with ALL. (author)

  14. Genetic variation in the extended major histocompatibility complex and susceptibility to childhood acute lymphoblastic leukemia: a review of the evidence

    Directory of Open Access Journals (Sweden)

    Kevin Y Urayama

    2013-12-01

    Full Text Available The enduring suspicion that infections and immunologic response may play a role in the etiology of childhood leukemia, particularly acute lymphoblastic leukemia (ALL, is now supported, albeit still indirectly, by numerous epidemiological studies. The cumulative evidence includes, for example, descriptive observations of a peculiar peak incidence at age 2-5 years for ALL in economically developed countries, clustering of cases in situations of population mixing associated with unusual patterns of personal contacts, associations with various proxy measures for immune modulatory exposures early in life, and genetic susceptibility conferred by variation in genes involved in the immune system. In this review, our focus is the extended major histocompatibility complex (xMHC, an approximately 7.6 megabase region that is well-known for its high density of expressed genes, extensive polymorphisms exhibiting complex linkage disequilibrium patterns, and its disproportionately large number of immune-related genes, including human leukocyte antigen (HLA. First discovered through the role they play in transplant rejection, the classical HLA class I (HLA-A, -B, and -C and class II (HLA-DR, HLA-DQ, and HLA-DP molecules reside at the epicenter of the immune response pathways and are now the targets of many disease susceptibility studies, including those for childhood leukemia. The genes encoding the HLA molecules are only a minority of the over 250 expressed genes in the xMHC, and a growing number of studies are beginning to evaluate other loci through targeted investigations or utilizing a mapping approach with a comprehensive screen of the entire region. Here, we review the current epidemiologic evidence available to date regarding genetic variation contained within this highly unique region of the genome and its relationship with childhood ALL risk.

  15. Translational profiling in childhood acute lymphoblastic leukemia: no evidence for glucocorticoid regulation of mRNA translation.

    Science.gov (United States)

    Aneichyk, Tatsiana; Bindreither, Daniel; Mantinger, Christine; Grazio, Daniela; Goetsch, Katrin; Kofler, Reinhard; Rainer, Johannes

    2013-12-01

    Glucocorticoids (GCs) are natural stress induced steroid hormones causing cell cycle arrest and cell death in lymphoid tissues. Therefore they are the central component in the treatment of lymphoid malignancies, in particular childhood acute lymphoblastic leukemia (chALL). GCs act mainly via regulating gene transcription, which has been intensively studied by us and others. GC control of mRNA translation has also been reported but has never been assessed systematically. In this study we investigate the effect of GCs on mRNA translation on a genome-wide scale. Childhood T- (CCRF-CEM) and precursor B-ALL (NALM6) cells were exposed to GCs and subjected to "translational profiling", a technique combining sucrose-gradient fractionation followed by Affymetrix Exon microarray analysis of mRNA from different fractions, to assess the translational efficiency of the expressed genes. Analysis of GC regulation in ribosome-bound fractions versus transcriptional regulation revealed no significant differences, i.e., GC did not entail a significant shift between ribosomal bound and unbound mRNAs. In the present study we analyzed for the first time possible effects of GC on the translational efficiency of expressed genes in two chALL model systems employing whole genome polysome profiling. Our results did not reveal significant differences in translational efficiency of expressed genes thereby arguing against a potential widespread regulatory effect of GCs on translation at least in the investigated in vitro systems.

  16. High resolution melting curve analysis, a rapid and affordable method for mutation analysis in childhood acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Yin eLiu

    2014-09-01

    Full Text Available Background: Molecular genetic alterations with prognostic significance have been described in childhood acute myeloid leukemia (AML. The aim of this study was to establish cost-effective techniques to detect mutations of FMS-like tyrosine kinase 3 (FLT3, Nucleophosmin 1 (NPM1, and a partial tandem duplication within the mixed lineage leukemia (MLL-PTD genes in childhood AML. Procedure: Ninety-nine children with newly diagnosed AML were included in this study. We developed a fluoresent dye SYTO-82 based high resolution melting curve (HRM anaylsis to detect FLT3 internal tandem duplication (FLT3-ITD, FLT3 tyrosine kinase domain (FLT3-TKD and NPM1 mutations. MLL-PTD was screened by real-time quantitative PCR. Results: The HRM methodology correlated well with gold standard Sanger sequencing with less cost. Among the 99 patients studied, the FLT3-ITD mutation was associated with significantly worse event free survival (EFS. Patients with the NPM1 mutation had significantly better EFS and overall survival. However, HRM was not sensitive enough for minimal residual disease monitoring. Conclusions: HRM was a rapid and efficient method for screening of FLT3 and NPM1 gene mutations. It was both affordable and accurate, especially in resource underprivileged regions. Our results indicated that HRM could be a useful clinical tool for rapid and cost effective screening of the FLT3 and NPM1 mutations in AML patients.

  17. High rate of non-response and relapse associated with peginterferon-alfa monotherapy for the treatment of acute hepatitis C in HIV-infected patients

    NARCIS (Netherlands)

    Arends, J.E.; Van Assen, S.; Wensing, A.J.; Stek, C.; Mudrikova, T.; Van Baarle, D.; Sprenger, H.G.; Hoepelman, A.

    2010-01-01

    Background: The incidence of acute hepatitis C virus infection (HCV) in patients infected with human immunodeficiency virus (HIV) is rising. Because of low patient numbers and a wide variety of inclusion criteria between studies, the optimal treatment regimen is under debate. We advocated

  18. Genomics in childhood acute myeloid leukemia comes of age | Office of Cancer Genomics

    Science.gov (United States)

    TARGET investigator’s study of nearly 1,000 pediatric acute myeloid leukemia (AML) cases reveals marked differences between the genomic landscapes of pediatric and adult AML and offers directions for future work.

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  20. 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

  1. Multiple Sclerosis Relapses: Epidemiology, Outcomes and Management. A Systematic Review.

    Science.gov (United States)

    Kalincik, Tomas

    2015-01-01

    Relapses (episodic exacerbations of neurological signs or symptoms) are a defining feature of relapsing-remitting multiple sclerosis (MS), the most prevalent MS phenotype. While their diagnostic value relates predominantly to the definition of clinically definite MS, their prognostic value is determined by their relatively high associated risk of incomplete remission resulting in residual disability. The mechanisms governing a relapse incidence are unknown, but numerous modifiers of relapse risk have been described, including demographic and clinical characteristics, many of which represent opportunities for improved disease management. Also relapse phenotypes have been associated with patient and disease characteristics and an individual predisposition to certain phenotypic presentations may imply individual neuroanatomical disease patterns. While immunomodulatory therapies and corticosteroids represent the mainstay of relapse prevention and acute management, respectively, their effect has only been partial and further search for more efficient relapse therapies is warranted. Other areas of research include pathophysiology and determinants of relapse incidence, recurrence and phenotypes, including the characteristics of the relapsing and non-relapsing multiple sclerosis variants and their responsiveness to therapies. © 2015 S. Karger AG, Basel.

  2. Severe childhood malnutrition.

    Science.gov (United States)

    Bhutta, Zulfiqar A; Berkley, James A; Bandsma, Robert H J; Kerac, Marko; Trehan, Indi; Briend, André

    2017-09-21

    The main forms of childhood malnutrition occur predominantly in children malnutrition. Here, we use the term 'severe malnutrition' to describe these conditions to better reflect the contributions of chronic poverty, poor living conditions with pervasive deficits in sanitation and hygiene, a high prevalence of infectious diseases and environmental insults, food insecurity, poor maternal and fetal nutritional status and suboptimal nutritional intake in infancy and early childhood. Children with severe malnutrition have an increased risk of serious illness and death, primarily from acute infectious diseases. International growth standards are used for the diagnosis of severe malnutrition and provide therapeutic end points. The early detection of severe wasting and kwashiorkor and outpatient therapy for these conditions using ready-to-use therapeutic foods form the cornerstone of modern therapy, and only a small percentage of children require inpatient care. However, the normalization of physiological and metabolic functions in children with malnutrition is challenging, and children remain at high risk of relapse and death. Further research is urgently needed to improve our understanding of the pathophysiology of severe malnutrition, especially the mechanisms causing kwashiorkor, and to develop new interventions for prevention and treatment.

  3. VCAM-1 and ICAM-1 serum levels as markers of relapse in visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Alexandros Makis

    2017-01-01

    Full Text Available Objectives-Methods. Visceral leishmaniasis (VL is characterized by chronicity and relapses despite efficacious treatment. Acute and chronic inflammatory processes and concomitant disturbances in cell adhesion characterize the pathogenesis of the disease. To investigate these processes further we measured adhesion molecules (L-selectin, ICAM-1 and VCAM-1 serum levels in 16 children with VL, as well as in 20 healthy controls. All children were treated with liposomal amphotericin B (3 mg/kg on days 1 to 5, 14, and 21. Measurements were performed at days 0, 15 and 30. Results. All children responded well to treatment in both clinical and laboratory terms. In three cases relapse occurred at 3, 5 and 6 months after treatment had ended. Serum L-selectin levels, both pre-treatment and post-treatment, did not significantly differ between patients and controls. VCAM-1 and ICAM-1 median levels were similar in patients and controls (P>0.05 at day 0 and significantly increased at day 15 (P0.05, but not in the 3 patients who relapsed (P<0.05. Conclusions. Despite the small number of the patients, the changes in VCAM-1 and ICAM-1 levels indicate the anti-parasite activation of the immune system during the course of VL and the effect of treatment. Decline in post-treatment serum VCAM-1 and ICAM-1 levels might be used as a marker of treatment efficacy in childhood VL.

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

    Directory of Open Access Journals (Sweden)

    Martin Feller

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

  5. Sarcocystis nesbitti causes acute, relapsing febrile myositis with a high attack rate: description of a large outbreak of muscular sarcocystosis in Pangkor Island, Malaysia, 2012.

    Directory of Open Access Journals (Sweden)

    Claire M Italiano

    2014-05-01

    Full Text Available BACKGROUND: From the 17th to 19th January 2012, a group of 92 college students and teachers attended a retreat in a hotel located on Pangkor Island, off the west coast of Peninsular Malaysia. Following the onset of symptoms in many participants who presented to our institute, an investigation was undertaken which ultimately identified Sarcocystis nesbitti as the cause of this outbreak. METHODOLOGY/PRINCIPAL FINDINGS: All retreat participants were identified, and clinical and epidemiological information was obtained via clinical review and self-reported answers to a structured questionnaire. Laboratory, imaging and muscle biopsy results were evaluated and possible sources of exposure, in particular water supply, were investigated. At an average of 9-11 days upon return from the retreat, 89 (97% of the participants became ill. A vast majority of 94% had fever with 57% of these persons experiencing relapsing fever. Myalgia was present in 91% of patients. Facial swelling from myositis of jaw muscles occurred in 9 (10% patients. The median duration of symptoms was 17 days (IQR 7 to 30 days; range 3 to 112. Out of 4 muscle biopsies, sarcocysts were identified in 3. S. nesbitti was identified by PCR in 3 of the 4 biopsies including one biopsy without observed sarcocyst. Non-Malaysians had a median duration of symptoms longer than that of Malaysians (27.5 days vs. 14 days, p = 0.001 and were more likely to experience moderate or severe myalgia compared to mild myalgia (83.3% vs. 40.0%, p = 0.002. CONCLUSIONS/SIGNIFICANCE: The similarity of the symptoms and clustered time of onset suggests that all affected persons had muscular sarcocystosis. This is the largest human outbreak of sarcocystosis ever reported, with the specific Sarcocystis species identified. The largely non-specific clinical features of this illness suggest that S. nesbitti may be an under diagnosed infection in the tropics.

  6. Sarcocystis nesbitti causes acute, relapsing febrile myositis with a high attack rate: description of a large outbreak of muscular sarcocystosis in Pangkor Island, Malaysia, 2012.

    Science.gov (United States)

    Italiano, Claire M; Wong, Kum Thong; AbuBakar, Sazaly; Lau, Yee Ling; Ramli, Norlisah; Syed Omar, Sharifah Faridah; Kahar Bador, Maria; Tan, Chong Tin

    2014-05-01

    From the 17th to 19th January 2012, a group of 92 college students and teachers attended a retreat in a hotel located on Pangkor Island, off the west coast of Peninsular Malaysia. Following the onset of symptoms in many participants who presented to our institute, an investigation was undertaken which ultimately identified Sarcocystis nesbitti as the cause of this outbreak. All retreat participants were identified, and clinical and epidemiological information was obtained via clinical review and self-reported answers to a structured questionnaire. Laboratory, imaging and muscle biopsy results were evaluated and possible sources of exposure, in particular water supply, were investigated. At an average of 9-11 days upon return from the retreat, 89 (97%) of the participants became ill. A vast majority of 94% had fever with 57% of these persons experiencing relapsing fever. Myalgia was present in 91% of patients. Facial swelling from myositis of jaw muscles occurred in 9 (10%) patients. The median duration of symptoms was 17 days (IQR 7 to 30 days; range 3 to 112). Out of 4 muscle biopsies, sarcocysts were identified in 3. S. nesbitti was identified by PCR in 3 of the 4 biopsies including one biopsy without observed sarcocyst. Non-Malaysians had a median duration of symptoms longer than that of Malaysians (27.5 days vs. 14 days, p = 0.001) and were more likely to experience moderate or severe myalgia compared to mild myalgia (83.3% vs. 40.0%, p = 0.002). The similarity of the symptoms and clustered time of onset suggests that all affected persons had muscular sarcocystosis. This is the largest human outbreak of sarcocystosis ever reported, with the specific Sarcocystis species identified. The largely non-specific clinical features of this illness suggest that S. nesbitti may be an under diagnosed infection in the tropics.

  7. Quality of health in survivors of childhood acute myeloid leukemia treated with chemotherapy only

    DEFF Research Database (Denmark)

    Molgaard-Hansen, Lene; Glosli, Heidi; Jahnukainen, Kirsi

    2011-01-01

    More than 60% of children with acute myeloid leukemia (AML) become long-term survivors, and approximately 50% are cured with chemotherapy only. Limited data exist about their long-term morbidity and social outcomes. The aim of the study was to compare the self-reported use of health care services...

  8. Pubertal development and fertility in survivors of childhood acute myeloid leukemia treated with chemotherapy only

    DEFF Research Database (Denmark)

    Molgaard-Hansen, Lene; Skou, Anne-Sofie; Juul, Anders

    2013-01-01

    More than 60% of children with acute myeloid leukemia (AML) become long-term survivors. Most are cured using chemotherapy without hematopoietic stem cell transplantation (HSCT). We report on pubertal development and compare self-reported parenthood among AML survivors and their siblings....

  9. 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.

  10. Symptom Differences in Acute and Chronic Presentation of Childhood Post-Traumatic Stress Disorder.

    Science.gov (United States)

    Famularo, Richard; And Others

    1990-01-01

    Twenty-four child abuse victims, age 5-13, were diagnosed with posttraumatic stress disorder (PTSD). Children with the acute form of PTSD exhibited such symptoms as difficulty falling asleep, hypervigilance, nightmares, and generalized anxiety. Children exhibiting chronic PTSD exhibited increased detachment, restricted range of affect,…

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

    DEFF Research Database (Denmark)

    Kapoor, Sarika; Marwaha, Ram; Majumdar, Siddhartha

    2007-01-01

    acute lymphoblastic leukemia (ALL) as compared to cells from children with non-hematological disorders ("Controls"). MAA recognized a 66 kDa sialoglycoprotein present in membrane fraction of ALL cells. Moreover, MAA induced apoptosis in ALL cells was found to be reduced significantly in presence of GM2...

  12. Hyperglycemia during induction therapy is associated with increased infectious complications in childhood acute lymphocytic leukemia

    Science.gov (United States)

    Children with acute lymphocytic leukemia (ALL) are at high risk for developing hyperglycemia. Hyperglycemic adult ALL patients have shorter remissions, more infections, and increased mortality. No corresponding data are available in children. We hypothesized that children with ALL who become hypergl...

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

    NARCIS (Netherlands)

    Plasschaert, Sabine Louise Anne

    2005-01-01

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

  14. 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...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi ...

  16. 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...

  17. The effect of central nervous system involvement and irradiation in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Taskinen, Mervi; Oskarsson, Trausti; Levinsen, Mette

    2017-01-01

    BACKGROUND: Central nervous system irradiation (CNS-RT) has played a central role in the cure of acute lymphoblastic leukemia (ALL), but due to the risk of long-term toxicity, it is now considered a less-favorable method of CNS-directed therapy. PROCEDURES: Retrospectively, we estimated the effect...

  18. Screening for acute childhood malnutrition during the National Nutrition Week in mali increases treatment referrals.

    Directory of Open Access Journals (Sweden)

    Daniele H Nyirandutiye

    Full Text Available OBJECTIVE: To evaluate a pilot intervention designed to integrate mid-upper arm circumference (MUAC screening for acute malnutrition into the semi-annual Child Nutrition Week (Semaine d'Intensification des Activités de Nutrition, or "SIAN" activities carried out in June 2008. DESIGN: A cross-sectional survey was conducted in Kolokani and Nara, two health districts in the Koulikoro region of Mali, 4-5 months after the SIAN, using a population-proportionate, multi-stage random sample of: 1 health centers, and 2 households in communities linked to each of the selected health centers. Caregivers of 1543 children who were 6-59 months of age at the time of the SIAN, 17 community-based volunteers and 45 health center staff members were interviewed. RESULTS: A total of 1278 children 6-59 months (83% of those studied reportedly participated in SIAN. Of the participating children, 1258 received vitamin A (98% of SIAN participants; 82% of all eligible children, 945 received anti-helminth tablets (84% of participants; 71% of eligibles, and 669 were screened for acute malnutrition (52% of participants; 43% of eligibles. 186 of the children screened (27% were reportedly identified as acutely malnourished. SIAN screening covered a significantly greater proportion of children than were examined in both community-based (22% of children and health center-based screening activities (5% of children combined during the 4-5 months after the SIAN (P<0.0001. In general, community volunteers and health personnel positively evaluated their experience adding MUAC screening to SIAN. CONCLUSION: Integrating MUAC screening for acute malnutrition in SIAN permits the assessment of a large number of children for acute malnutrition, and should be continued.

  19. Screening for Acute Childhood Malnutrition during the National Nutrition Week in Mali Increases Treatment Referrals

    Science.gov (United States)

    Nyirandutiye, Daniele H.; Ag Iknane, Akory; Fofana, Amadou; Brown, Kenneth H.

    2011-01-01

    Objective To evaluate a pilot intervention designed to integrate mid-upper arm circumference (MUAC) screening for acute malnutrition into the semi-annual Child Nutrition Week (Semaine d'Intensification des Activités de Nutrition, or “SIAN”) activities carried out in June 2008. Design A cross-sectional survey was conducted in Kolokani and Nara, two health districts in the Koulikoro region of Mali, 4–5 months after the SIAN, using a population-proportionate, multi-stage random sample of: 1) health centers, and 2) households in communities linked to each of the selected health centers. Caregivers of 1543 children who were 6–59 months of age at the time of the SIAN, 17 community-based volunteers and 45 health center staff members were interviewed. Results A total of 1278 children 6–59 months (83% of those studied) reportedly participated in SIAN. Of the participating children, 1258 received vitamin A (98% of SIAN participants; 82% of all eligible children), 945 received anti-helminth tablets (84% of participants; 71% of eligibles), and 669 were screened for acute malnutrition (52% of participants; 43% of eligibles). 186 of the children screened (27%) were reportedly identified as acutely malnourished. SIAN screening covered a significantly greater proportion of children than were examined in both community-based (22% of children) and health center-based screening activities (5% of children) combined during the 4-5 months after the SIAN (P<0.0001). In general, community volunteers and health personnel positively evaluated their experience adding MUAC screening to SIAN. Conclusion Integrating MUAC screening for acute malnutrition in SIAN permits the assessment of a large number of children for acute malnutrition, and should be continued. PMID:21731602

  20. Crisis management in the treatment of childhood acute lymphoblastic leukemia: putting right what can go wrong (emergency complications of disease and treatment).

    Science.gov (United States)

    Hough, Rachael; Vora, Ajay

    2017-12-08

    The improvement in overall survival in children with acute lymphoblastic leukemia (ALL) over the last 5 decades has been considerable, with around 90% now surviving long term. The risk of relapse has been reduced to such an extent that the risk of treatment-related mortality is now approaching that of mortality caused by relapse. Toxicities may also lead to the suboptimal delivery of chemotherapy (treatment delays, dose reductions, dose omissions), potentially increasing relapse risk, and short- and long-term morbidity, adding to the "burden of therapy" in an increasing number of survivors. Thus, the need to reduce toxicity in pediatric ALL is becoming increasingly important. This work focuses on the risk factors, pathogenesis, clinical features, and emergency management of the life-threatening complications of ALL at presentation and during subsequent chemotherapy, including leucostasis, tumor lysis syndrome, infection, methotrexate encephalopathy, thrombosis, and pancreatitis. Potential strategies to abrogate these toxicities in the future are also discussed. © 2016 by The American Society of Hematology. All rights reserved.

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

    Science.gov (United States)

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

    2017-09-01

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

  2. 4-aminopyridyl-based lead compounds targeting CYP51 prevent spontaneous parasite relapse in a chronic model and improve cardiac pathology in an acute model of Trypanosoma cruzi infection.

    Science.gov (United States)

    Calvet, Claudia Magalhaes; Choi, Jun Yong; Thomas, Diane; Suzuki, Brian; Hirata, Ken; Lostracco-Johnson, Sharon; de Mesquita, Liliane Batista; Nogueira, Alanderson; Meuser-Batista, Marcelo; Silva, Tatiana Araujo; Siqueira-Neto, Jair Lage; Roush, William R; de Souza Pereira, Mirian Claudia; McKerrow, James H; Podust, Larissa M

    2017-12-01

    Chagas disease, caused by the protozoan Trypanosoma cruzi, is the leading cause of heart failure in Latin America. The clinical treatment of Chagas disease is limited to two 60 year-old drugs, nifurtimox and benznidazole, that have variable efficacy against different strains of the parasite and may lead to severe side effects. CYP51 is an enzyme in the sterol biosynthesis pathway that has been exploited for the development of therapeutics for fungal and parasitic infections. In a target-based drug discovery program guided by x-ray crystallography, we identified the 4-aminopyridyl-based series of CYP51 inhibitors as being efficacious versus T.cruzi in vitro; two of the most potent leads, 9 and 12, have now been evaluated for toxicity and efficacy in mice. Both acute and chronic animal models infected with wild type or transgenic T. cruzi strains were evaluated. There was no evidence of toxicity in the 28-day dosing study of uninfected animals, as judged by the monitoring of multiple serum and histological parameters. In two acute models of Chagas disease, 9 and 12 drastically reduced parasitemia, increased survival of mice, and prevented liver and heart injury. None of the compounds produced long term sterile cure. In the less severe acute model using the transgenic CL-Brenner strain of T.cruzi, parasitemia relapsed upon drug withdrawal. In the chronic model, parasitemia fell to a background level and, as evidenced by the bioluminescence detection of T. cruzi expressing the red-shifted luciferase marker, mice remained negative for 4 weeks after drug withdrawal. Two immunosuppression cycles with cyclophosphamide were required to re-activate the parasites. Although no sterile cure was achieved, the suppression of parasitemia in acutely infected mice resulted in drastically reduced inflammation in the heart. The positive outcomes achieved in the absence of sterile cure suggest that the target product profile in anti-Chagasic drug discovery should be revised in favor of

  3. Relapse of nephrotic syndrome during post-rituximab peripheral blood B-lymphocyte depletion.

    Science.gov (United States)

    Sato, Mai; Kamei, Koichi; Ogura, Masao; Ishikura, Kenji; Ito, Shuichi

    2018-02-01

    Rituximab is effective against complicated childhood steroid-dependent nephrotic syndrome (SDNS). Peripheral blood B-lymphocyte (B-cell) depletion is strongly correlated with persistent remission, relapse rarely occurring during B-cell depletion; however, we have encountered several such patients. We retrospectively analyzed the characteristics and clinical course of 82 patients with SDNS treated with rituximab from January 2007 to December 2012 in our institution. Six of 82 patients (7.3%) had relapses during B-cell depletion after receiving rituximab (relapsed group). The remaining 76 patients did not have relapses during B-cell depletion (non-relapsed group). The median time to initial relapse during B-cell depletion was 85 days after receiving rituximab, which is significantly shorter than in the non-relapsed group (410 days, p = 0.0003). The median annual numbers of relapses after receiving rituximab were 2.5 and 0.9 in the relapsed and non-relapsed groups, respectively (p depletion did not differ between the two groups. Relapse during B-cell depletion after receiving rituximab suggests that various pathophysiological mechanisms play a part in childhood nephrotic syndrome.

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

    International Nuclear Information System (INIS)

    Porter, Rosalyn P.; Kaste, Sue C.

    2004-01-01

    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.)

  5. 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.)

  6. Long-Term Effect of Cranial Radiotherapy on Pituitary-Hypothalamus Area in Childhood Acute Lymphoblastic Leukemia Survivors.

    Science.gov (United States)

    Follin, Cecilia; Erfurth, Eva Marie

    2016-09-01

    Survival rates of childhood cancer have improved markedly, and today more than 80 % of those diagnosed with a pediatric malignancy will become 5-year survivors. Nevertheless, survivors exposed to cranial radiotherapy (CRT) are at particularly high risk for long-term morbidity, such as endocrine insufficiencies, metabolic complications, and cardiovascular morbidity. Deficiencies of one or more anterior pituitary hormones have been described following therapeutic CRT for primary brain tumors, nasopharyngeal tumors, and following prophylactic CRT for childhood acute lymphoblastic leukemia (ALL). Studies have consistently shown a strong correlation between the total radiation dose and the development of pituitary deficits. Further, age at treatment and also time since treatment has strong implications on pituitary hormone deficiencies. There is evidence that the hypothalamus is more radiosensitive than the pituitary and is damaged by lower doses of CRT. With doses of CRT hypothalamus and this usually causes isolated GH deficiency (GHD). Higher doses (>50 Gy) may produce direct anterior pituitary damage, which contributes to multiple pituitary deficiencies. The large group of ALL survivors treated with CRT in the 70-80-ties has now reached adulthood, and these survivors were treated mainly with 24 Gy, and the vast majority of these patients suffer from GHD. Further, after long-term follow-up, insufficiencies in prolactin (PRL) and thyroid stimulating hormone (TSH) have also been reported and a proportion of these patients were also adrenocoticotrophic hormone (ACTH) deficient. CRT to the hypothalamus causes neuroendocrine dysfunction, which means that the choice of GH test is crucial for the diagnosis of GHD.

  7. Severe acute malnutrition in childhood: hormonal and metabolic status at presentation, response to treatment, and predictors of mortality.

    Science.gov (United States)

    Bartz, Sarah; Mody, Aaloke; Hornik, Christoph; Bain, James; Muehlbauer, Michael; Kiyimba, Tonny; Kiboneka, Elizabeth; Stevens, Robert; Bartlett, John; St Peter, John V; Newgard, Christopher B; Freemark, Michael

    2014-06-01

    Malnutrition is a major cause of childhood morbidity and mortality. To identify and target those at highest risk, there is a critical need to characterize biomarkers that predict complications prior to and during treatment. We used targeted and nontargeted metabolomic analysis to characterize changes in a broad array of hormones, cytokines, growth factors, and metabolites during treatment of severe childhood malnutrition. Children aged 6 months to 5 years were studied at presentation to Mulago Hospital and during inpatient therapy with milk-based formulas and outpatient supplementation with ready-to-use food. We assessed the relationship between baseline hormone and metabolite levels and subsequent mortality. Seventy-seven patients were enrolled in the study; a subset was followed up from inpatient treatment to the outpatient clinic. Inpatient and outpatient therapies increased weight/height z scores and induced striking changes in the levels of fatty acids, amino acids, acylcarnitines, inflammatory cytokines, and various hormones including leptin, insulin, GH, ghrelin, cortisol, IGF-I, glucagon-like peptide-1, and peptide YY. A total of 12.2% of the patients died during hospitalization; the major biochemical factor predicting mortality was a low level of leptin (P = .0002), a marker of adipose tissue reserve and a critical modulator of immune function. We have used metabolomic analysis to provide a comprehensive hormonal and metabolic profile of severely malnourished children at presentation and during nutritional rehabilitation. Our findings suggest that fatty acid metabolism plays a central role in the adaptation to acute malnutrition and that low levels of the adipose tissue hormone leptin associate with, and may predict, mortality prior to and during treatment.

  8. Second allogeneic hematopoietic SCT for relapsed ALL in children.

    Science.gov (United States)

    Kato, M; Horikoshi, Y; Okamoto, Y; Takahashi, Y; Hasegawa, D; Koh, K; Takita, J; Inoue, M; Kigasawa, H; Ogawa, A; Sasahara, Y; Kawa, K; Yabe, H; Sakamaki, H; Suzuki, R; Kato, K

    2012-10-01

    A second SCT is generally accepted as the only potentially curative approach for ALL patients that relapse after SCT, but the role of second SCT for pediatric ALL is not fully understood. We performed a retrospective analysis of 171 pediatric patients who received a second allo-SCT for relapsed ALL after allo-SCT. OS at 2 years was 29.4 ± 3.7%, the cumulative incidence of relapse was 44.1 ± 4.0% and non-relapse mortality was 18.8 ± 3.5%. Relapse occurred faster after the second SCT than after the first SCT (117 days vs 164 days, P=0.04). Younger age (9 years or less), late relapse (180 days or more after first SCT), CR at the second SCT, and myeloablative conditioning were found to be related to longer survival. Neither acute GVHD nor the type of donor influenced the outcome of second SCT. Multivariate analysis showed that younger age and late relapse were associated with better outcomes. Our analysis suggests that second SCT for relapsed pediatric ALL is an appropriate treatment option for patients that have achieved CR, which is associated with late relapse after the first SCT.

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

    OpenAIRE

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

    2015-01-01

    Abstract To assess the self-esteem of pediatric patients on chemotherapy for acute lymphoblastic leukemia (ALL) and psychological status of their parents. The psychological status of 178 children receiving chemotherapy for ALL and their parents was assessed using parenting stress index (PSI) to determine the degree of stress the parents are exposed to using parent's and child's domains. Self-esteem Scale was used to determine the psychological status of patients. The study revealed significan...

  10. Screening for acute childhood malnutrition during the National Nutrition Week in mali increases treatment referrals.

    Science.gov (United States)

    Nyirandutiye, Daniele H; Ag Iknane, Akory; Fofana, Amadou; Brown, Kenneth H

    2011-01-01

    To evaluate a pilot intervention designed to integrate mid-upper arm circumference (MUAC) screening for acute malnutrition into the semi-annual Child Nutrition Week (Semaine d'Intensification des Activités de Nutrition, or "SIAN") activities carried out in June 2008. A cross-sectional survey was conducted in Kolokani and Nara, two health districts in the Koulikoro region of Mali, 4-5 months after the SIAN, using a population-proportionate, multi-stage random sample of: 1) health centers, and 2) households in communities linked to each of the selected health centers. Caregivers of 1543 children who were 6-59 months of age at the time of the SIAN, 17 community-based volunteers and 45 health center staff members were interviewed. A total of 1278 children 6-59 months (83% of those studied) reportedly participated in SIAN. Of the participating children, 1258 received vitamin A (98% of SIAN participants; 82% of all eligible children), 945 received anti-helminth tablets (84% of participants; 71% of eligibles), and 669 were screened for acute malnutrition (52% of participants; 43% of eligibles). 186 of the children screened (27%) were reportedly identified as acutely malnourished. SIAN screening covered a significantly greater proportion of children than were examined in both community-based (22% of children) and health center-based screening activities (5% of children) combined during the 4-5 months after the SIAN (Pmalnutrition in SIAN permits the assessment of a large number of children for acute malnutrition, and should be continued.

  11. Pubertal development and fertility in survivors of childhood acute myeloid leukemia treated with chemotherapy only: a NOPHO-AML study.

    Science.gov (United States)

    Molgaard-Hansen, Lene; Skou, Anne-Sofie; Juul, Anders; Glosli, Heidi; Jahnukainen, Kirsi; Jarfelt, Marianne; Jónmundsson, Guðmundur K; Malmros, Johan; Nysom, Karsten; Hasle, Henrik

    2013-12-01

    More than 60% of children with acute myeloid leukemia (AML) become long-term survivors. Most are cured using chemotherapy without hematopoietic stem cell transplantation (HSCT). We report on pubertal development and compare self-reported parenthood among AML survivors and their siblings. We included 137 children treated for AML according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO)-AML-84, -88, and -93 trials, who were alive by June 2007. Patients with relapse or treated with HSCT were excluded. AML survivors participated in a physical and biochemical examination (n = 102) and completed a questionnaire (n = 101). One of their siblings completed an identical questionnaire (n = 84). At a median follow-up of 11 years (range 5-25) after diagnosis of AML the survivors (median age 16 years, range 5-36) were either prepubertal or had entered puberty normally. Serum levels of FSH, LH, testosterone, estradiol, sex hormone binding globulin (SHBG), inhibin A and B, and testicular volumes were within normal ranges. Anti-Müllerian hormone (AMH) levels were decreased in 5 of 40 postpubertal females. Mean reported age at menarche was 13.1 (range 11-17) years. Among survivors 15 years of age or older 31% of females reported pregnancies and 9% of males reported pregnancies in their partners, rates comparable with the frequency reported by their siblings. Most AML survivors treated with chemotherapy had normal pubertal development and fertility, however, AMH levels were decreased in 13% of postpubertal females. Longer follow-up is necessary to evaluate possible risk of premature ovarian failure. © 2013 Wiley Periodicals, Inc.

  12. Child symptoms, parent behaviors, and family strain in long-term survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Huang, I-Chan; Brinkman, Tara M; Mullins, Larry; Pui, Ching-Hon; Robison, Leslie L; Hudson, Melissa M; Krull, Kevin R

    2018-05-17

    How family environment and parental factors affect health status and symptoms in childhood cancer survivors is understudied. We examined the influence of family cohesion, parent distress, and overprotection on child symptom burden and health-related quality of life (HRQOL) and family strain in survivors of childhood acute lymphoblastic leukemia (ALL). Parents of 213 children treated with chemotherapy-only completed a survey when survivors were at least five-years post-diagnosis. Family Environment Scale, Brief Symptom Inventory-18, Parent Protection Scale, PedsQL, and Impact on Family were used to assess family cohesion, parental distress, overprotection, child symptom burden and HRQOL, and family strain, respectively. Path analysis was conducted to quantify effects of family cohesion on family strain through parental distress, overprotection, child symptoms, and HRQOL. Lower family cohesion (β=0.06, 95% CI=0.01 to 0.13), higher parental distress (β=0.35, 95% CI=0.20 to 0.45), and overprotection (β=0.17, 95% CI=0.01 to 0.32) were associated with more child symptom burden. More symptom burden were associated with poorer child HRQOL (β=0.66, 95% CI=0.57 to 0.75), which in turn was associated with more family strain (β=0.11, 95% CI=0.01 to 0.22). Lower maternal education was associated with overprotection (β=-0.23, 95% CI=-0.33 to -0.12), more child symptoms (β=-0.30, 95% CI=-0.41 to -0.16), poorer child HRQOL (β=-0.36, 95% CI=-0.46 to -0.21), and more family strain (β=-0.15, 95% CI=-0.23 to -0.08). Family and parental factors contributed to health outcomes of childhood ALL survivors. Interventions to enhance family cohesion, decrease parental distress and overprotection, and ameliorate child symptoms may improve family functioning. This article is protected by copyright. All rights reserved.

  13. Childhood Acute Respiratory Infections and Household Environment in an Eastern Indonesian Urban Setting

    Directory of Open Access Journals (Sweden)

    Tomoyuki Shibata

    2014-11-01

    Full Text Available This pilot study evaluated the potential effect of household environmental factors such as income, maternal characteristics, and indoor air pollution on children’s respiratory status in an Eastern Indonesian community. Household data were collected from cross-sectional (n = 461 participants and preliminary childhood case-control surveys (pneumonia cases = 31 diagnosed within three months at a local health clinic; controls = 30. Particulate matter (PM2.5 and PM10 was measured in living rooms, kitchens, children’s bedrooms, and outside areas in close proximity once during the case-control household interviews (55 homes and once per hour from 6 a.m. to midnight in 11 homes. The household survey showed that children were 1.98 times (p = 0.02 more likely to have coughing symptoms indicating respiratory infection, if mothers were not the primary caregivers. More children exhibited coughing if they were not exclusively breastfed (OR = 2.18; p = 0.06 or there was a possibility that their mothers were exposed to environmental tobacco smoke during pregnancy (OR = 2.05; p = 0.08. This study suggests that household incomes and mother’s education have an indirect effect on childhood pneumonia and respiratory illness. The concentrations of PM2.5 and PM10 ranged from 0.5 to 35.7 µg/m3 and 7.7 to 575.7 µg/m3, respectively, based on grab samples. PM was significantly different between the case and control groups (p < 0.01. The study also suggests that ambient air may dilute indoor pollution, but also introduces pollution into the home from the community environment. Effective intervention programs need to be developed that consider multiple direct and indirect risk factors to protect children.

  14. Relapse or Recurrence

    Science.gov (United States)

    ... Childhood Cancer Statistics Webinars Video Library Types of Children’s Cancer Leukemia Lymphoma Solid Tumors (Sarcomas) More… During Treatment Tests and Procedures Treatment Options Treatment Side Effects ...

  15. Translational Phase I Trial of Vorinostat (Suberoylanilide Hydroxamic Acid) Combined with Cytarabine and Etoposide in Patients with Relapsed, Refractory, or High-Risk Acute Myeloid Leukemia

    Science.gov (United States)

    Gojo, Ivana; Tan, Ming; Fang, Hong-Bin; Sadowska, Mariola; Lapidus, Rena; Baer, Maria R.; Carrier, France; Beumer, Jan H.; Anyang, Bean N.; Srivastava, Rakesh K.; Espinoza-Delgado, Igor; Ross, Douglas D.

    2015-01-01

    Purpose To determine the maximum-tolerated dose (MTD) of the histone deacetylase inhibitor vorinostat combined with fixed doses of cytarabine (ara-C or cytosine arabinoside) and etoposide in patients with poor-risk or advanced acute leukemia, to obtain preliminary efficacy data, describe pharmacokinetics, and in vivo pharmacodynamic effects of vorinostat in leukemia blasts. Experimental Design In this open-label phase I study, vorinostat was given orally on days one to seven at three escalating dose levels: 200 mg twice a day, 200 mg three times a day, and 300 mg twice a day. On days 11 to 14, etoposide (100 mg/m2) and cytarabine (1 or 2 g/m2 twice a day if ≥65 or vorinostat 200 mg twice a day. Of 21 patients enrolled, seven attained a complete remission (CR) or CR with incomplete platelet recovery, including six of 13 patients treated at the MTD. The median remission duration was seven months. No differences in percentage S-phase cells or multidrug resistance transporter (MDR1 or BCRP) expression or function were observed in vivo in leukemia blasts upon vorinostat treatment. Conclusions Vorinostat 200 mg twice a day can be given safely for seven days before treatment with cytarabine and etoposide. The relatively high CR rate seen at the MTD in this poor-risk group of patients with AML warrants further studies to confirm these findings. PMID:23403629

  16. Seizure characteristics of epilepsy in childhood after acute encephalopathy with biphasic seizures and late reduced diffusion.

    Science.gov (United States)

    Ito, Yuji; Natsume, Jun; Kidokoro, Hiroyuki; Ishihara, Naoko; Azuma, Yoshiteru; Tsuji, Takeshi; Okumura, Akihisa; Kubota, Tetsuo; Ando, Naoki; Saitoh, Shinji; Miura, Kiyokuni; Negoro, Tamiko; Watanabe, Kazuyoshi; Kojima, Seiji

    2015-08-01

    The aim of this study was to clarify characteristics of post-encephalopathic epilepsy (PEE) in children after acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), paying particular attention to precise diagnosis of seizure types. Among 262 children with acute encephalopathy/encephalitis registered in a database of the Tokai Pediatric Neurology Society between 2005 and 2012, 44 were diagnosed with AESD according to the clinical course and magnetic resonance imaging (MRI) findings and were included in this study. Medical records were reviewed to investigate clinical data, MRI findings, neurologic outcomes, and presence or absence of PEE. Seizure types of PEE were determined by both clinical observation by pediatric neurologists and ictal video-electroencephalography (EEG) recordings. Of the 44 patients after AESD, 10 (23%) had PEE. The period between the onset of encephalopathy and PEE ranged from 2 to 39 months (median 8.5 months). Cognitive impairment was more severe in patients with PEE than in those without. Biphasic seizures and status epilepticus during the acute phase of encephalopathy did not influence the risk of PEE. The most common seizure type of PEE on clinical observation was focal seizures (n = 5), followed by epileptic spasms (n = 4), myoclonic seizures (n = 3), and tonic seizures (n = 2). In six patients with PEE, seizures were induced by sudden unexpected sounds. Seizure types confirmed by ictal video-EEG recordings were epileptic spasms and focal seizures with frontal onset, and all focal seizures were startle seizures induced by sudden acoustic stimulation. Intractable daily seizures remain in six patients with PEE. We demonstrate seizure characteristics of PEE in children after AESD. Epileptic spasms and startle focal seizures are common seizure types. The specific seizure types may be determined by the pattern of diffuse subcortical white matter injury in AESD and age-dependent reorganization of the brain

  17. Relapsing polychondritis: commentary

    Directory of Open Access Journals (Sweden)

    R.D. Altman

    2011-09-01

    Full Text Available Relapsing Polychondritis (RP is a multisystem disease of unknown etiology characterized by episodic inflammation of cartilage and potentially progressive degeneration of cartilaginous tissue, such as auricular, nasal and laryngotracheobronchial cartilage. However, many other proteoglycan- rich structures may be involved, such as inner ear, eyes, blood vessels, heart and kidneys (1- 4. RP was first described by Jacksh-Wartenhorst in 1923, who named it “polychondropathia” (5. Pearson et al. (6 introduced the term “relapsing polychondritis” in 1960...

  18. Identification of de Novo Fanconi Anemia in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia

    Science.gov (United States)

    2016-05-13

    Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Fanconi Anemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  19. Diapers in war zones: ethnomedical factors in acute childhood gastroenteritis in Peshawar, Pakistan.

    Directory of Open Access Journals (Sweden)

    Saira H Zaidi

    Full Text Available This article considers ethnomedical knowledge and practices among parents related to contraction of acute gastroenteritis among children in Peshawar, Pakistan. Research methods included analysis of the Emergency Pediatric Services' admission register, a structured interview administered to 47 parents of patients seen in the Khyber Medical College Teaching Hospital, semi-structured interviews of 12 staff, and four home visits among families with children treated at the hospital. The use of native research assistants and participant observation contributed to the reliability of the findings, though the ethnographic, home-visit sample is small. Our research indicated that infection rates are exacerbated in homes through two culturally salient practices and one socioeconomic condition. Various misconceptions propagate the recurrence or perserverance of acute gastroenteritis including assumptions about teething leading to poor knowledge of disease etiology, rehydration solutions leading to increased severity of disease, and diaper usage leading to the spread of disease. In our Discussion, we suggest how hospital structures of authority and gender hierarchy may impact hospital interactions, the flow of information, and its respective importance to the patient's parents leading to possible propagation of disease. These ethnographic data offer a relatively brief but targeted course of action to improve the effectiveness of prevention and treatment efforts.

  20. Human parvovirus B19 in childhood acute lymphoblastic leukaemia in Basrah.

    Science.gov (United States)

    Ibrahem, Wijdan Nazar; Hasony, Hassan Jaber; Hassan, Jenan Ghulam

    2014-01-01

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

  1. 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...... pronounced when B cell precursor and T cell leukemia were analyzed separately (B cell precursor ALL: MRD-PI vs prednisolone LC50: n = 33, rs = 0.47, P = 0.006; T cell ALL: MRD-PI vs prednisolone resistance: n = 8, rs = 0.84, P = 0.009). After a median follow-up of 5.0 years (75% range 3.2-6.9) eight patients...

  2. Extremely low-frequency magnetic fields and childhood acute lymphoblastic leukemia: an exploratory analysis of alternative exposure metrics.

    Science.gov (United States)

    Auvinen, A; Linet, M S; Hatch, E E; Kleinerman, R A; Robison, L L; Kaune, W T; Misakian, M; Niwa, S; Wacholder, S; Tarone, R E

    2000-07-01

    Data collected by the National Cancer Institute-Children's Cancer Group were utilized to explore various metrics of magnetic field levels and risk of acute lymphoblastic leukemia (ALL) in children. Cases were aged 0-14 years, were diagnosed with ALL during 1989-1993, were registered with the Children's Cancer Group, and resided in one home for at least 70 percent of the 5 years immediately prior to diagnosis. Controls were identified by using random digit dialing and met the same residential requirements. With 30-second ("spot") measurements and components of the 24-hour measurement obtained in the subject's bedroom, metrics evaluated included measures of central tendency, peak exposures, threshold values, and measures of short-term temporal variability. Measures of central tendency and the threshold measures showed good-to-high correlation, but these metrics correlated less well with the others. Small increases in risk (ranging from 1.02 to 1.69 for subjects in the highest exposure category) were associated with some measures of central tendency, but peak exposures, threshold values, measures of short-term variability, and spot measurements demonstrated little association with risk of childhood ALL. In general, risk estimates were slightly higher for the nighttime (10 p.m.-6 a.m.) interval than for the corresponding 24-hour period.

  3. Acute and long-term cytogenetic effects of treatment in childhood cancer

    International Nuclear Information System (INIS)

    Aronson, M.M.; Miller, R.C.; Hill, R.B.; Nichols, W.W.; Meadows, A.T.

    1982-01-01

    The incidence of chromosomal aberrations in banded karyotypes and of sister-chromatid exchanges (SCEs) was determined in the lymphocytes of survivors of childhood cancer as 2 parameters which are pertinent in assessing the genetic damage induced by chemotherapy. The proportion of cells with chromosome breakage or structural rearrangement-type aberration was 1 cell in 67 in a control group of 8 untreated cancer patients and 2 parents of cancer patients, 1 cell in 8 in 12 patients currently on therapy, and 1 cell in 50 in 17 patients sampled 6 months to 35 years post-treatment. The range of mean SCE levels per cell was 4.5-6.5 in the untreated cancer patients, 4.0-9.6 in non-cancer controls, 3.3-33.7 in patients on therapy, and 4.6-9.7 in post-therapy survivors. Considerable variability was observed between individuals with both SCE and breakage assays but therapy-induced increases in SCEs were not necessarily correlated with increased levels of aberrations arising from chromosomal breakage. (orig.)

  4. MRI diagnosis of bone marrow relapse in children with ALL

    International Nuclear Information System (INIS)

    Kan, J.H.; Hernanz-Schulman, Marta; Frangoul, Haydar A.; Connolly, Susan A.

    2008-01-01

    Diffuse marrow replacement in acute leukemia is well known, but there are few reports describing the MRI features of pediatric leukemic relapse. Our purpose was to describe the MRI appearance of pediatric leukemic relapse. A total of 53 consecutive children with a history of ALL were referred for musculoskeletal MRI from 1 January 1998 to 28 February 2007 at one center, and from 1 January 2000 to 2 May 2007 at a second center. From this group, 14 children seen at initial diagnosis of leukemia and 2 children who underwent MRI after therapy for relapse were excluded. The remaining 37 children, 8 with relapse and 29 in remission, were studied. Images of patients with relapse and in remission were reviewed for type and configuration of marrow infiltration; coexisting marrow alterations including osteonecrosis or stress reaction were also reviewed. All eight children with relapse demonstrated nodular lesions with well-defined margins. Coexisting osteonecrosis was present in three children (38%) and pathologic fracture in one. Among the 29 children in remission, 9 showed stress reaction/fracture, 14 showed osteonecrosis and 9 showed ill-defined nodules, and in 5 the marrow was completely normal. Well-defined nodules in all patients with leukemic relapse suggest that this appearance is characteristic and distinct from the published findings of diffuse marrow replacement in acute leukemia. (orig.)

  5. MRI diagnosis of bone marrow relapse in children with ALL

    Energy Technology Data Exchange (ETDEWEB)

    Kan, J.H.; Hernanz-Schulman, Marta [Vanderbilt University, Department of Radiology and Radiological Sciences, Vanderbilt Children' s Hospital, Nashville, TN (United States); Frangoul, Haydar A. [Vanderbilt University, Department of Pediatric Hematology-Oncology, Vanderbilt Children' s Hospital, Nashville, TN (United States); Connolly, Susan A. [Harvard Medical School, Department of Radiology, Boston Children' s Hospital, Boston, MA (United States)

    2008-01-15

    Diffuse marrow replacement in acute leukemia is well known, but there are few reports describing the MRI features of pediatric leukemic relapse. Our purpose was to describe the MRI appearance of pediatric leukemic relapse. A total of 53 consecutive children with a history of ALL were referred for musculoskeletal MRI from 1 January 1998 to 28 February 2007 at one center, and from 1 January 2000 to 2 May 2007 at a second center. From this group, 14 children seen at initial diagnosis of leukemia and 2 children who underwent MRI after therapy for relapse were excluded. The remaining 37 children, 8 with relapse and 29 in remission, were studied. Images of patients with relapse and in remission were reviewed for type and configuration of marrow infiltration; coexisting marrow alterations including osteonecrosis or stress reaction were also reviewed. All eight children with relapse demonstrated nodular lesions with well-defined margins. Coexisting osteonecrosis was present in three children (38%) and pathologic fracture in one. Among the 29 children in remission, 9 showed stress reaction/fracture, 14 showed osteonecrosis and 9 showed ill-defined nodules, and in 5 the marrow was completely normal. Well-defined nodules in all patients with leukemic relapse suggest that this appearance is characteristic and distinct from the published findings of diffuse marrow replacement in acute leukemia. (orig.)

  6. Acute Disseminated Encephalomyelitis: A Review of Eleven Cases in Childhood in North of Iran

    Directory of Open Access Journals (Sweden)

    Ali Nikkhah

    2016-01-01

    Full Text Available Background: Acute disseminated encephalomyelitis (ADEM is an inflammatory demyelinating disorder. The pathogenesis is unclear, but it is thought to be immune-mediated. The prognosis is favorable, with most children making a full recovery. Objectives: The present report analyzed different clinical presentations, response to treatment and outcome in a series of 11 patients with ADEM who referred to our tertiary center in north of Iran from 2010 to 2014. Materials and Methods: In this retrospective simple descriptive review, eleven cases with ADEM admitted in the neurology ward from 2010 to 2014 were enrolled. The clinical findings and laboratory and imaging results of patients were reviewed. All of these cases were evaluated with neurological examination, serologic tests for bacterial meningitis and viral encephalitis (especially, herpes simplex virus and brain MRI without contrast. After discharge, patients were followed for at least six months (6 to 12 months clinically and radiologically. Results: Of 11 children, 8 were male and 3 female. Their ages ranged between 4 and 10 years. The mean interval between the preceding infection and symptoms of encephalomyelitis was nine days. The most common presenting symptoms were ataxia in 45.4%, fever and headache in 36.4% and altered consciousness in 18.2% of patients. Neurological examination revealed pyramidal motor signs such as brisk deep tendon reflexes (hyperreflexia (81.8%, cranial nerve involvement (18.2%, dysarthria (9.1% and abnormal movements (9.1%. We followed up these patients in long-term for 6 to 12 months. Only in 1 child who received IVIG, mild ataxia had reminded. Conclusions: The prognosis of acute disseminated encephalomyelitis (ADEM is favorable. Early diagnosis and prompt treatment of ADEM would probably reduce morbidity.

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

    International Nuclear Information System (INIS)

    Ibrahem, W.N.; Hasony, H.J.; Hassan, J.G.

    2014-01-01

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

  8. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Clinicians Publications for Your Patients MS Navigator Program Programs and Services for Your Patients Contact Us Clinical Fellows ... Relapsing-remitting MS (RRMS) Relapsing-remitting ...

  9. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... for You and Your Practice Publications for Clinicians Publications for Your Patients MS Navigator Program Programs and Services for Your Patients ... Relapsing-remitting MS (RRMS) Relapsing-remitting MS ( ...

  10. Recurrence and Relapse in Bipolar Mood Disorder

    Directory of Open Access Journals (Sweden)

    S Gh Mousavi

    2004-06-01

    Full Text Available Background: Despite the effectiveness of pharmacotherapy in acute phase of bipolar mood disorder, patients often experience relapses or recurrent episodes. Hospitalization of patients need a great deal of financial and humanistic resources which can be saved through understanding more about the rate of relapse and factors affecting this rate. Methods: In a descriptive analytical study, 380 patients with bipolar disorder who were hospitalized in psychiatric emergency ward of Noor hospital, Isfahan, Iran, were followed. Each patient was considered for; the frequency of relapse and recurrence, kind of pharmachotherapy, presence of psychotherapeutic treatments, frequency of visits by psychiatrist and the rank of present episode. Results: The overall prevalence of recurrence was 42.2%. Recurrence was lower in patients using lithium carbonate or sodium valproate or combined therapy (about 40%, compared to those using carbamazepine (80%. Recurrence was higher in patients treated with only pharmacotherapy (44.5% compared to those treated with both pharmacotherapy and psychotherapy (22.2%. Patients who were visited monthy by psychiatrist had lower rate of recurrence compared to those who had irregular visits. Conclusion: The higher rate of recurrence observed in carbamazepine therapy may be due to its adverse reactions and consequently poor compliance to this drug. Lower rates of recurrence with psychotherapy and regular visits may be related to the preventive effects of these procedures and especially to the effective management of stress. Keywords: Bipolar Mood Disorder, Recurrence, Relapse.

  11. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... MS Relapsing-remitting MS (RRMS) Share this page Facebook Twitter Email Relapsing-remitting MS (RRMS) Relapsing-remitting ... Here Start Here Colophon Stay Informed Join Us Facebook Twitter LinkedIn YouTube Pinterest MS Connection About the ...

  12. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Relapsing-remitting MS (RRMS) Share this page Facebook Twitter Email Relapsing-remitting MS (RRMS) Relapsing-remitting MS ( ... Start Here Colophon Stay Informed Join Us Facebook Twitter LinkedIn YouTube Pinterest MS Connection About the Society ...

  13. The development of cerebral CT changes during treatment of acute lymphocytic leukemia in childhood

    International Nuclear Information System (INIS)

    Pedersen, H.; Clausen, N.

    1981-01-01

    Twenty-three children with acute lymphocytic leukemia (ALL) were examined with cranial CT at least twice with a minimal interval of 10 months. The first CT was performed at the time of diagnosis in 11 children and during therapy in 12; all but two were normal on the first CT examination. These two had slight enlargement of the ventricular system and subarachnoid space at the time of diagnosis. These findings were unchanged on the second CT examinations. Seven patients, all in remission from leukemia of the central nervous system manifested abnormal findings on later CTs. Low density areas in the periventricular white matter were seen in the brains of three, with increasing subcortical calcification in one of these cases. Five children had slight enlargement of the ventricular system and subarachnoid space, especially of the basal and Sylvian cisterns. Later CT examinations in five, plus brain autopsy in two cases, revealed unchanged or progressive conditions. The CT findings have been related to the treatment and some characteristics of the disease. The frequency of CT abnormalities was higher in patients who had received therapeutic irradiation and intraventricular methotrexate treatment. The possible reasons for the CT abnormalities are discussed. (orig.)

  14. Changes in cytogenetics and molecular genetics in acute myeloid leukemia from childhood to adult age groups.

    Science.gov (United States)

    Creutzig, Ursula; Zimmermann, Martin; Reinhardt, Dirk; Rasche, Mareike; von Neuhoff, Christine; Alpermann, Tamara; Dworzak, Michael; Perglerová, Karolína; Zemanova, Zuzana; Tchinda, Joelle; Bradtke, Jutta; Thiede, Christian; Haferlach, Claudia

    2016-12-15

    To obtain better insight into the biology of acute myeloid leukemia (AML) in various age groups, this study focused on the genetic changes occurring during a lifetime. This study analyzed the relation between age and genetics from birth to 100 years in 5564 patients with de novo AML diagnosed from 1998 to 2012 (1192 patients from nationwide pediatric studies [AML Berlin-Frankfurt-Münster studies 98 and 2004] and 4372 adults registered with the Munich Leukemia Laboratory). The frequencies of cytogenetic subgroups were age-dependent. Favorable subtypes (t(8;21), inv(16)/t(16;16), and t(15;17)) decreased in general from the pediatric age group (2 to groups ( 70 years; P age-specific incidence with age. Interestingly, the frequency of 11q23 abnormalities decreased from infants to older patients. The proportion of clinically relevant molecular aberrations of CCAAT/enhancer binding protein α, nucleophosmin (NPM1), and NPM1/fms-related tyrosine kinase 3-internal tandem duplication increased with age. Altogether, with the exclusion of infants, a significant decrease in the proportion of favorable cytogenetic subtypes and an increase in unfavorable cytogenetics were observed with increasing age. These findings indicate different mechanisms for the pathogenesis of AML; these different mechanisms also suggest directions for etiological research and contribute to the more unfavorable prognosis with increasing age. Cancer 2016;122:3821-3830. © 2016 American Cancer Society. © 2016 American Cancer Society.

  15. Increased Body Mass Index during Therapy for Childhood Acute Lymphoblastic Leukemia: A Significant and Underestimated Complication

    Directory of Open Access Journals (Sweden)

    Helen C. Atkinson

    2015-01-01

    Full Text Available Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL and treated with modern COG protocols (n=80 to determine longitudinal changes in body mass index (BMI and the prevalence of obesity compared with a healthy reference population. Results. At diagnosis, the majority of patients (77.5% were in the healthy weight category. During treatment, increases in BMI z-scores were greater for females than males; the prevalence of obesity increased from 10.3% to 44.8% (P<0.004 for females but remained relatively unchanged for males (9.8% to 13.7%, P=0.7. Longitudinal analysis using linear mixed-effects identified associations between BMI z-scores and time-dependent interactions with sex (P=0.0005, disease risk (P<0.0001, age (P=0.0001, and BMI z-score (P<0.0001 at diagnosis and total dose of steroid during maintenance (P=0.01. Predicted mean BMI z-scores at the end of therapy were greater for females with standard risk ALL irrespective of age at diagnosis and for males younger than 4 years of age at diagnosis with standard risk ALL. Conclusion. Females treated on standard risk protocols and younger males may be at greatest risk of becoming obese during treatment for ALL. These subgroups may benefit from intervention strategies to manage BMI during treatment for ALL.

  16. Rotavirus and other enteropathogens in childhood acute diarrhoea: a study of two centres in Malaysia.

    Science.gov (United States)

    Lee, Way S; Rajasekaran, Ganeswrie; Pee, Susan; Karunakaran, Rina; Hassan, Hamimah H; Puthucheary, Savithri D

    2006-09-01

    To study the role of rotavirus in children hospitalised for acute gastroenteritis (AGE) in two urban hospitals in Malaysia. A 12-month prospective study (January to December 2002), in children younger than 14 years with AGE hospitalised to the paediatric units of University of Malaya Medical Centre (UMMC), Kuala Lumpur; and Hospital Sultanah Aminah (HSA), Johor Bahru, Malaysia was conducted. In 2002, 399 and 1307 children with AGE were admitted to UMMC and HSA, respectively. Two hundred and eighty-eight (72%) stool samples from UMMC and 901 (69%) samples from HSA were analysed. Rotavirus was the most common aetiological agent identified in both centres (average 32%; UMMC 35%, HSA 30%, P = 0.94). The peak age group for rotavirus-related hospitalisation was 24-35 months for UMMC and 12-23 months for HSA. Nine percent of patients hospitalised for rotavirus infection in UMMC and 22% of patients in HSA were older than 5 years of age. An outbreak of rotavirus infection within the communities served by both centres resulting in an increase in hospital admissions of rotavirus gastroenteritis was observed in both units from January to March 2002. The peak age group for rotavirus-related hospital admission in this study was much older, between 12 to 35 months. It is uncertain whether this was related to the outbreak of rotavirus gastroenteritis observed within two urban areas from January to March 2002 causing re-infection with rotavirus in older children.

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

    Science.gov (United States)

    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

  18. Impact of genetic polymorphisms on chemotherapy toxicity in childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Guillermo eGervasini

    2012-11-01

    Full Text Available The efficacy of chemotherapy in pediatric acute lymphoblastic leukemia (ALL patients has significantly increased in the last twenty years; as a result, the focus of research is slowly shifting from trying to increase survival rates to reduce chemotherapy-related toxicity.At the present time, the cornerstone of therapy for ALL is still formed by a reduced number of drugs with a highly toxic profile. In recent years, a number of genetic polymorphisms have been identified that can play a significant role in modifying the pharmacokinetics and pharmacodynamics of these drugs. The best example is that of the TPMT gene, whose genotyping is being incorporated to clinical practice in order to individualize doses of mercaptopurine. However, there are additional genes that are relevant for the metabolism, activity and/or transport of other chemotherapy drugs that are widely use in ALL, such as methotrexate, cyclophosphamide, vincristine, L-asparaginase, etoposide, cytarabine or cytotoxic antibiotics. These genes can also be affected by genetic alterations that could therefore have clinical consequences.In this review we will discuss recent data on this field, with special focus on those polymorphisms that could be used in clinical practice to tailor chemotherapy for ALL in order to reduce the occurrence of serious adverse effects.

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

    Science.gov (United States)

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

    2015-12-01

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

  20. Childhood acute pyelonephritis: comparison of power Doppler sonography and Tc-DMSA scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Stogianni, Aggeliki; Oikonomou, Ippoliti; Dimitriadis, Athanasios [Aristotle University of Thessaloniki, Department of Radiology, AHEPA Hospital, Thessaloniki (Greece); Nikolopoulos, Panagiotis [424 Army Hospital, Department of Radiology, Thessaloniki (Greece); Gatzola, Magdalini [Aristotle University of Thessaloniki, 2nd Paediatric Clinic, AHEPA Hospital, Thessaloniki (Greece); Balaris, Vassilios [Aristotle University of Thessaloniki, Department of Nuclear Medicine, AHEPA Hospital, Thessaloniki (Greece); Farmakiotis, Dimitrios [Infectious Diseases Hospital of Thessaloniki, Department of Medicine, Thessaloniki (Greece)

    2007-07-15

    Tc 99m DMSA scintigraphy is regarded as the gold standard for the detection and localization of acute pyelonephritis (APN) in children. Power Doppler sonography (PD US) is a radiation-free and cost-effective technique that could be useful in the diagnosis of APN in children. To compare the predictive value of PD US with DMSA scintigraphy in the diagnosis of APN in children. A total of 74 neonates and children with clinical findings consistent with possible upper urinary tract infection were evaluated with PD US and DMSA scintigraphy. Children with anatomic (grey-scale) abnormalities were excluded. A total of 147 kidneys were examined within the first 48 h after the onset of symptoms. Each kidney was divided into three zones (upper, middle, and lower third). APN was diagnosed by PD US in 46 kidneys. Sensitivity and specificity for detecting APN using DMSA scintigraphy as the reference standard were 73.8% and 85.7%, respectively. There was good agreement between PD US and DMSA scintigraphy in the localization of lesions. In clinically suspected APN, PD US has acceptable specificity and sensitivity, if performed within the first 48 h and could be helpful in neonates and children under 3 months of age in whom the use of scintigraphy is generally discouraged. (orig.)

  1. Anthropometry in Long-Term Survivors of Acute Lymphoblastic Leukemia in Childhood and Adolescence.

    Science.gov (United States)

    Collins, Laura; Beaumont, Lesley; Cranston, Amy; Savoie, Stefanie; Nayiager, Trishana; Barr, Ronald

    2017-06-01

    Body mass index (BMI) is an inadequate measure of nutritional status in children and adolescents with cancer as it does not distinguish muscle from adipose tissue. However, arm anthropometry offers simple assessments of fat mass and lean body mass; especially valuable in low- and middle-income countries where the great majority of young people with cancer live and access to sophisticated expensive measures of body composition is markedly limited. The nutritional status of 75 long-term survivors of acute lymphoblastic leukemia was assessed by arm anthropometry, in addition to BMI, in a cross-sectional cohort study. Normal ranges for triceps skin fold thickness (TSFT, a surrogate for fat mass) and mid-upper arm circumference (MUAC, a surrogate for lean body mass) were between the 15th and 85th percentiles for age and sex. Overweight/obesity was classified as a TSFT >85th percentile and sarcopenia as an MUAC obesity was identified in 1/3 of subjects by a BMI >25 and by TSFT; and 20% of the subjects had a TSFT >95th percentile. Only two subjects were sarcopenic. None met the combined criteria for sarcopenic obesity. TSFT and MUAC/height indices did not add sensitivity to identification of sarcopenia or obesity. TSFT is a useful measure of overweight/obesity in this population, but MUAC does not identify a notable proportion with sarcopenia. Further resolution may be provided by more sophisticated measures of body composition.

  2. Promoter DNA methylation pattern identifies prognostic subgroups in childhood T-cell acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Magnus Borssén

    Full Text Available BACKGROUND: Treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL has improved, but there is a considerable fraction of patients experiencing a poor outcome. There is a need for better prognostic markers and aberrant DNA methylation is a candidate in other malignancies, but its potential prognostic significance in T-ALL is hitherto undecided. DESIGN AND METHODS: Genome wide promoter DNA methylation analysis was performed in pediatric T-ALL samples (n = 43 using arrays covering >27000 CpG sites. Clinical outcome was evaluated in relation to methylation status and compared with a contemporary T-ALL group not tested for methylation (n = 32. RESULTS: Based on CpG island methylator phenotype (CIMP, T-ALL samples were subgrouped as CIMP+ (high methylation and CIMP- (low methylation. CIMP- T-ALL patients had significantly worse overall and event free survival (p = 0.02 and p = 0.001, respectively compared to CIMP+ cases. CIMP status was an independent factor for survival in multivariate analysis including age, gender and white blood cell count. Analysis of differently methylated genes in the CIMP subgroups showed an overrepresentation of transcription factors, ligands and polycomb target genes. CONCLUSIONS: We identified global promoter methylation profiling as being of relevance for subgrouping and prognostication of pediatric T-ALL.

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

    Directory of Open Access Journals (Sweden)

    Anna Mikosik

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

  4. Spectrum of centrosome autoantibodies in childhood varicella and post-varicella acute cerebellar ataxia

    Directory of Open Access Journals (Sweden)

    Stinton Laura M

    2003-09-01

    Full Text Available Abstract Background Sera from children with post-varicella infections have autoantibodies that react with centrosomes in brain and tissue culture cells. We investigated the sera of children with infections and post-varicella ataxia and related conditions for reactivity to five recombinant centrosome proteins: γγ-enolase, pericentrin, ninein, PCM-1, and Mob1. Methods Sera from 12 patients with acute post-varicella ataxia, 1 with post-Epstein Barr virus (EBV ataxia, 5 with uncomplicated varicella infections, and other conditions were tested for reactivity to cryopreserved cerebellum tissue and recombinant centrosome proteins. The distribution of pericentrin in the cerebellum was studied by indirect immunofluorescence (IIF using rabbit antibodies to the recombinant protein. Antibodies to phospholipids (APL were detected by ELISA. Results Eleven of 12 children with post-varicella ataxia, 4/5 children with uncomplicated varicella infections, 1/1 with post-EBV ataxia, 2/2 with ADEM, 1/2 with neuroblastoma and ataxia, and 2/2 with cerebellitis had antibodies directed against 1 or more recombinant centrosome antigens. Antibodies to pericentrin were seen in 5/12 children with post-varicella ataxia but not in any of the other sera tested. IIF demonstrated that pericentrin is located in axons and centrosomes of cerebellar cells. APL were detected in 75% of the sera from children with post-varicella ataxia and 50% of children with varicella without ataxia and in none of the controls. Conclusion This is the first study to show the antigen specificity of anti-centrosome antibodies in children with varicella. Our data suggest that children with post-varicella ataxia have unique autoantibody reactivity to pericentrin.

  5. 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

  6. Impact of sleep, fatigue, and systemic inflammation on neurocognitive and behavioral outcomes in long-term survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Cheung, Yin Ting; Brinkman, Tara M; Mulrooney, Daniel A; Mzayek, Yasmin; Liu, Wei; Banerjee, Pia; Panoskaltsis-Mortari, Angela; Srivastava, Deokumar; Pui, Ching-Hon; Robison, Leslie L; Hudson, Melissa M; Krull, Kevin R

    2017-09-01

    Long-term survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for neurocognitive impairment, which may be associated with fatigue, sleep problems, systemic inflammation, and oxidative stress. We examined these associations among survivors of childhood ALL treated with chemotherapy only. Survivors of childhood ALL (male, n = 35 and female, n = 35; mean age, 14.3 years [standard deviation, 4.7 years] and mean years from diagnosis, 7.4 years [standard deviation, 1.9 years]) completed neurocognitive testing, behavioral ratings, and reported sleep quality and fatigue symptoms 5 years after diagnosis. Serum was collected concurrently and assayed for interleukin (IL)-1β and IL-6, tumor necrosis factor α (TNF-α), high-sensitivity C-reactive protein (hsCRP), malondialdehyde, myeloperoxidase, and oxidized low-density lipoprotein. General linear modeling was used to assess associations among biomarkers and functional outcomes, adjusting for age and stratified by sex. Survivors performed worse than population norms on executive function and processing speed and reported more behavioral problems (P fatigue was associated with poor executive function (r = 0.41; P = .02), processing speed (r = 0.56; P fatigue measures were observed. Neurocognitive function in female survivors of childhood ALL appears more susceptible to the effects of sleep disturbance and fatigue. Systemic inflammation may play a role in neurocognitive impairment and behavioral symptoms. Cancer 2017;123:3410-9. © 2017 American Cancer Society. © 2017 American Cancer Society.

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

    Science.gov (United States)

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

    2009-04-01

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

  8. Weight change during childhood acute lymphoblastic leukemia induction therapy predicts obesity: a report from the Children's Oncology Group.

    Science.gov (United States)

    Withycombe, Janice S; Smith, Lynette M; Meza, Jane L; Merkle, Carrie; Faulkner, Melissa Spezia; Ritter, Leslie; Seibel, Nita L; Moore, Ki

    2015-03-01

    Obesity is a well documented problem associated with childhood acute lymphoblastic leukemia (ALL) with increasing body mass index often observed during therapy. This study aims to evaluate if weight gain, early in therapy, is predictive of obesity at the end of treatment. In this secondary analysis, data from 1,017 high-risk ALL patients previously treated on a Children's Oncology Group protocol (CCG study 1961) were reviewed. Logistic regression was used to examine whether change in BMI z-score at Induction or Delayed Intensification (DI) 1 were predictive of obesity at the end of therapy. The BMI z-score at the beginning of Induction and the change in BMI z-score during Induction were both significant predictors of obesity at the end of therapy. The change in BMI z-score during cycle 1 of DI was not found to be associated with obesity. It is well know that obesity at the beginning of therapy is predictive of obesity at the end of ALL therapy. The new, and more important, finding from this study is that even after adjusting for baseline weight, the increase in BMI z-scores during induction was an independent predictor of obesity at the end of therapy. Most researchers agree that prevention is the best form of treatment for obesity as it is difficult to reverse once it is present. This study suggests that monitoring weight trends during Induction may be useful in guiding healthcare practitioners in identifying which patients are at highest risk for obesity development so that early intervention may occur. © 2014 Wiley Periodicals, Inc.

  9. Deficient innate immunity, thymopoiesis, and gene expression response to radiation in survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Leung, Wing; Neale, Geoffrey; Behm, Fred; Iyengar, Rekha; Finkelstein, David; Kastan, Michael B; Pui, Ching-Hon

    2010-06-01

    Survivors of childhood acute lymphoblastic leukemia (ALL) are at an increased risk of developing secondary malignant neoplasms. Radiation and chemotherapy can cause mutations and cytogenetic abnormalities and induce genomic instability. Host immunity and appropriate DNA damage responses are critical inhibitors of carcinogenesis. Therefore, we sought to determine the long-term effects of ALL treatment on immune function and response to DNA damage. Comparative studies on 14 survivors in first complete remission and 16 siblings were conducted. In comparison to siblings on the cells that were involved in adaptive immunity, the patients had either higher numbers (CD19+ B cells and CD4+CD25+ T regulatory cells) or similar numbers (alphabetaT cells and CD45RO+/RA- memory T cells) in the blood. In contrast, patients had lower numbers of all lymphocyte subsets involved in innate immunity (gammadeltaT cells and all NK subsets, including KIR2DL1+ cells, KIR2DL2/L3+ cells, and CD16+ cells), and lower natural cytotoxicity against K562 leukemia cells. Thymopoiesis was lower in patients, as demonstrated by less CD45RO-/RA+ naïve T cell and less SjTREC levels in the blood, whereas the Vbeta spectratype complexity score was similar. Array of gene expression response to low-dose radiation showed that about 70% of the probesets had a reduced response in patients. One of these genes, SCHIP-1, was also among the top-ranked single nucleotide polymorphisms (SNPs) during the whole-genome scanning by SNP microarray analysis. ALL survivors were deficient in innate immunity, thymopoiesis, and DNA damage responses to radiation. These defects may contribute to their increased likelihood of second malignancy. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  10. Prevalence and predictors of anxiety and depression after completion of chemotherapy for childhood acute lymphoblastic leukemia: A prospective longitudinal study

    Science.gov (United States)

    Kunin-Batson, Alicia S.; Lu, Xiaomin; Balsamo, Lyn; Graber, Kelsey; Devidas, Meenakshi; Hunger, Stephen P.; Carroll, William L.; Winick, Naomi J.; Mattano, Leonard A.; Maloney, Kelly W.; Kadan-Lottick, Nina S.

    2016-01-01

    Background The months immediately following completion of treatment for childhood acute lymphoblastic leukemia (ALL) are often regarded as a stressful time for children and families. In this prospective, longitudinal study, the prevalence and predictors of anxiety and depressive symptoms after completion of treatment were examined. Methods Participants included 160 children (ages 2-9 years) with standard-risk ALL enrolled on Children's Oncology Group protocol AALL0331. Parents completed standardized rating scales of children's emotional-behavioral functioning, and measures of coping and family functioning at ∼1, 6, and 12 months after diagnosis, and again 3 months following completion of chemotherapy. Results Three months off-therapy, 24% of survivors had at-risk/clinically elevated anxiety scores and 28% had elevated depression scores, significantly higher than the expected 15% in the general population (p=0.028 and 0.001, respectively). Patients with elevated anxiety one-month post-diagnosis were at greater risk for off–therapy anxiety (OR=4.1; 95% CI, 1.31-12.73, p=0.022), and those with elevated depressive symptoms 6-months post-diagnosis were at greater risk for off-therapy depression (OR=7.88, 95% CI, 2.61-23.81, p=0.0002). In adjusted longitudinal analyses, unhealthy family functioning (p=0.008), and less reliance on social support coping (p=0.009) were associated with risk for emotional distress. Children from Spanish-speaking families (p=0.05) were also at greater risk for distress. Conclusions A significant proportion of children experience emotional distress during and after therapy for ALL. These data provide a compelling rationale for targeted early screening, and psychosocial interventions to support family functioning and coping skills. PMID:27028090

  11. Impact of Socioeconomic Status on Timing of Relapse and Overall Survival for Children Treated on Dana-Farber Cancer Institute ALL Consortium Protocols (2000-2010).

    Science.gov (United States)

    Bona, Kira; Blonquist, Traci M; Neuberg, Donna S; Silverman, Lewis B; Wolfe, Joanne

    2016-06-01

    Population-based evidence suggests that lower socioeconomic status (SES) negatively impacts the overall survival (OS) of children with leukemia; however, the relationships between SES and treatment-related mortality, relapse, and timing of relapse remain unclear. We examined OS, event-free survival (EFS) and cumulative incidence (CI) and timing of relapse by community-level poverty for 575 children aged 1-18 years with newly diagnosed acute lymphoblastic leukemia (ALL) treated on consecutive phase III multicenter Dana-Farber Cancer Institute ALL Consortium Protocols between 2000 and 2010. Children were categorized into high- and low-poverty areas for the analysis using aggregate U.S. Census data linked to zip code. Children living in high-poverty areas experienced a 5-year OS of 85% as compared with 92% for those in low-poverty areas (P = 0.02); poverty remained marginally significant (P = 0.07) after adjustment for immunophenotype, age, and white blood cell count. There were no differences detected in EFS or CI relapse by poverty area. However, 92% of the relapses observed in children from high-poverty areas occurred <36 months from complete remission, compared to 48% of those in children from low-poverty areas (P = 0.008). U.S. children with ALL living in high-poverty areas have a higher risk of early relapse when compared with those living in low-poverty areas despite uniform treatment. This may in part explain decreased OS observed in these children. This finding highlights disparities in childhood cancer outcomes by SES despite uniform treatment. Further investigations of the mechanistic pathways underlying this finding are needed. © 2016 Wiley Periodicals, Inc.

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

    DEFF Research Database (Denmark)

    Vaitkeviciene, G; Forestier, E; Hellebostad, M

    2011-01-01

    Prognostic impact of peripheral blood white blood cell count (WBC) at the diagnosis of childhood acute lymphoblastic leukaemia (ALL) was evaluated in a population-based consecutive series of 2666 children aged 1–15 treated for ALL between 1992 and 2008 in the five Nordic countries (Denmark, Finland.......58) and for T-ALL (pEFS5y 0.71 vs. 0.38). Whether the inferior EFS for the subset of patients with high WBC and slow initial response to treatment reflects rare or overlooked cytogenetic aberrations as well as the factors that determine WBC levels at diagnosis awaits exploration....

  13. Hepatic sinusoidal obstruction syndrome during maintenance therapy of childhood acute lymphoblastic leukemia is associated with continuous asparaginase therapy and mercaptopurine metabolites

    DEFF Research Database (Denmark)

    Toksvang, Linea Natalie; De Pietri, Silvia; Nielsen, Stine N.

    2017-01-01

    BACKGROUND: Hepatic sinusoidal obstruction syndrome (SOS) during treatment of childhood acute lymphoblastic leukemia (ALL) has mainly been associated with 6-thioguanine. The occurrence of several SOS cases after the introduction of extended pegylated asparaginase (PEG-asparaginase) therapy...... in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol led us to hypothesize that PEG-asparaginase, combined with other drugs, may trigger SOS during 6-thioguanine-free maintenance therapy. PROCEDURE: In children with ALL treated in Denmark according to the NOPHO ALL2008 protocol...... children receiving PEG-asparaginase biweekly, 29 developed SOS (≥2 criteria: hyperbilirubinemia, hepatomegaly, ascites, weight gain ≥2.5%, unexplained thrombocytopenia

  14. In vitro cellular drug resistance adds prognostic information to other known risk-factors in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Lönnerholm, Gudmar; Thörn, Ingrid; Sundström, Christer

    2011-01-01

    Leukemic cells from 230 children with newly diagnosed B-cell precursor ALL were tested for in vitro drug resistance to a panel of anti-cancer drugs. Minimal residual disease (MRD) was measured by RQ-PCR. During follow-up, 24 relapses occurred in the 159 children with MRD...

  15. Recombinant EphB4-HSA Fusion Protein and Azacitidine or Decitabine for Relapsed or Refractory Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia Patients Previously Treated With a Hypomethylating Agent

    Science.gov (United States)

    2017-08-18

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Recurrent Adult Acute Myeloid Leukemia

  16. Social settings and addiction relapse.

    Science.gov (United States)

    Walton, M A; Reischl, T M; Ramanthan, C S

    1995-01-01

    Despite addiction theorists' acknowledgment of the impact of environmental factors on relapse, researchers have not adequately investigated these influences. Ninety-six substance users provided data regarding their perceived risk for relapse, exposure to substances, and involvement in reinforcing activities. These three setting attributes were assessed in their home, work, and community settings. Reuse was assessed 3 months later. When controlling for confounding variables, aspects of the home settings significantly distinguished abstainers from reusers; perceived risk for relapse was the strongest predictor of reuse. Exposure to substances and involvement in reinforcing activities were not robust reuse indicators. The work and community settings were not significant determinants of reuse. These findings offer some initial support for the utility of examining social settings to better understand addiction relapse and recovery. Identification of setting-based relapse determinants provides concrete targets for relapse prevention interventions.

  17. Support for social rehabilitation of childhood acute lymphoblastic leukemia patients. Psychological and educational assessment by the K-ABC

    Energy Technology Data Exchange (ETDEWEB)

    Izumi, Mayuko [Ochanomizu Univ., Tokyo (Japan); Hosoya, Ryouta; Oohira, Mutsuro; Kaneko, Takashi; Matsushita, Taketsugu

    2000-10-01

    Intellectual impairment in pediatric acute lymphoblastic leukemia (ALL) is thought to be caused by the effect of treatment on the central nervous system. We therefore assessed the characteristics and tendencies of patients' cognitive ability by using the K-ABC (Kaufman Assessment Battery for Children), an intelligence test. The subjects were 28 patients treated for ALL (males 18, females 10, age 4.7-12.0 years). The patients who took the K-ABC test were divided into irradiation group (15 patients who received brain irradiation as prophylactic treatment) and a non-irradiation group (13 patients whose brain was not irradiated), and evaluated the results. The K-ABC consists of a cognition processing scale and an acquisition level, and the cognition processing scale consists of a sequential processing scale and simultaneous processing scale. Patients were assessed in regard to various factors: 1. sex, 2. age of onset, 3. length of hospital stay, 4. age at the time of irradiation, 5. radiation dose, 6. score on the cognition processing scale, and multiple comparisons were made based on analysis of variance, least significant differences (1, 2, 3, 6), and the t-test (4, 5). Sequential processing ability was impaired in the patients with impaired cognitive processing in both groups. Part of simultaneous processing ability (ability to understand spatial relationships) tended to be reduced in the irradiation group in addition to the impairment in sequential processing ability, and factors 1 and 4 influenced cognitive ability in the irradiation group. The ability of girls decreased more than in boys. When children were irradiated below 4 years of age, their ability decreased even more. Regardless of whether they had received radiation therapy, all of the patients had received chemotherapy, including methotrexate, etc., and the anticancer drugs may have reduced their cognitive ability. The reduction of simultaneous processing ability may have been caused by the addition

  18. Support for social rehabilitation of childhood acute lymphoblastic leukemia patients. Psychological and educational assessment by the K-ABC

    International Nuclear Information System (INIS)

    Izumi, Mayuko; Hosoya, Ryouta; Oohira, Mutsuro; Kaneko, Takashi; Matsushita, Taketsugu

    2000-01-01

    Intellectual impairment in pediatric acute lymphoblastic leukemia (ALL) is thought to be caused by the effect of treatment on the central nervous system. We therefore assessed the characteristics and tendencies of patients' cognitive ability by using the K-ABC (Kaufman Assessment Battery for Children), an intelligence test. The subjects were 28 patients treated for ALL (males 18, females 10, age 4.7-12.0 years). The patients who took the K-ABC test were divided into irradiation group (15 patients who received brain irradiation as prophylactic treatment) and a non-irradiation group (13 patients whose brain was not irradiated), and evaluated the results. The K-ABC consists of a cognition processing scale and an acquisition level, and the cognition processing scale consists of a sequential processing scale and simultaneous processing scale. Patients were assessed in regard to various factors: 1. sex, 2. age of onset, 3. length of hospital stay, 4. age at the time of irradiation, 5. radiation dose, 6. score on the cognition processing scale, and multiple comparisons were made based on analysis of variance, least significant differences (1, 2, 3, 6), and the t-test (4, 5). Sequential processing ability was impaired in the patients with impaired cognitive processing in both groups. Part of simultaneous processing ability (ability to understand spatial relationships) tended to be reduced in the irradiation group in addition to the impairment in sequential processing ability, and factors 1 and 4 influenced cognitive ability in the irradiation group. The ability of girls decreased more than in boys. When children were irradiated below 4 years of age, their ability decreased even more. Regardless of whether they had received radiation therapy, all of the patients had received chemotherapy, including methotrexate, etc., and the anticancer drugs may have reduced their cognitive ability. The reduction of simultaneous processing ability may have been caused by the addition of

  19. Remitting - Relapsing Polyneuropathy In Juvenile Metachromatic Leukodystrophy

    Directory of Open Access Journals (Sweden)

    Taly AB

    2004-01-01

    Full Text Available A five-year-old girl manifested with acute relapsing polyradiculo-neuropathy. Elevated cerebrospinal fluid proteins, electro-physiological evidence of conduction block and remitting course suggested possible acquired demyelinating radiculoneuropathy. However, intellectual deterioration during follow up, evidence of extensive, symmetrical and periventricular demyelination on MRI of brain and metachromatic on sural nerve biopsy led to the diagnosis of metachromatic leukodystrophy (MLD. Inherited neuropathies such as MLD may occasionally present atypically in the early stages. Recognition of this variation has considerable therapeutic and prognostic significance.

  20. Influence of IL15 gene variations on the clinical features, treatment response and risk of developing childhood acute lymphoblastic leukemia in Latvian population.

    Science.gov (United States)

    Rots, Dmitrijs; Kreile, Madara; Nikulshin, Sergejs; Kovalova, Zhanna; Gailite, Linda

    2018-02-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Modern treatment protocols allow achievement of long-term event-free survival rates in up to 85% of cases, although the treatment response varies among different patient groups. It is hypothesized that treatment response is influenced by the IL15 gene variations, although research results are conflicting. To analyze IL15 gene variations influence treatment response, clinical course and the risk of developing ALL we performed a case-control and family-based study. The study included 81 patients with childhood ALL. DNA samples of both or one biological parent were available for 62 of ALL patients and 130 age and gender adjusted healthy samples were used as a control group. Analyzed IL15 gene variations: rs10519612, rs10519613 and rs17007695 were genotyped using PCR-RFLP assay. Our results shows that IL15 gene variations haplotypes are associated with the risk of developing childhood ALL (p variations separately. The variations rs10519612 and rs1059613 in a recessive pattern of inheritance were associated with hyperdiploidy (p = 0.048). Analyzed genetic variations had no impact on other clinical features and treatment response (assessed by the minimal residual disease) in our study.

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

    DEFF Research Database (Denmark)

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

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

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

    Science.gov (United States)

    2017-07-19

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

  3. Differences in meiotic recombination rates in childhood acute lymphoblastic leukemia at an MHC class II hotspot close to disease associated haplotypes.

    Directory of Open Access Journals (Sweden)

    Pamela Thompson

    Full Text Available Childhood Acute Lymphoblastic Leukemia (ALL is a malignant lymphoid disease of which B-cell precursor- (BCP and T-cell- (T ALL are subtypes. The role of alleles encoded by major histocompatibility loci (MHC have been examined in a number of previous studies and results indicating weak, multi-allele associations between the HLA-DPB1 locus and BCP-ALL suggested a role for immunosusceptibility and possibly infection. Two independent SNP association studies of ALL identified loci approximately 37 kb from one another and flanking a strong meiotic recombination hotspot (DNA3, adjacent to HLA-DOA and centromeric of HLA-DPB1. To determine the relationship between this observation and HLA-DPB1 associations, we constructed high density SNP haplotypes of the 316 kb region from HLA-DMB to COL11A2 in childhood ALL and controls using a UK GWAS data subset and the software PHASE. Of four haplotype blocks identified, predicted haplotypes in Block 1 (centromeric of DNA3 differed significantly between BCP-ALL and controls (P = 0.002 and in Block 4 (including HLA-DPB1 between T-ALL and controls (P = 0.049. Of specific common (>5% haplotypes in Block 1, two were less frequent in BCP-ALL, and in Block 4 a single haplotype was more frequent in T-ALL, compared to controls. Unexpectedly, we also observed apparent differences in ancestral meiotic recombination rates at DNA3, with BCP-ALL showing increased and T-ALL decreased levels compared to controls. In silico analysis using LDsplit sotware indicated that recombination rates at DNA3 are influenced by flanking loci, including SNPs identified in childhood ALL association studies. The observed differences in rates of meiotic recombination at this hotspot, and potentially others, may be a characteristic of childhood leukemia and contribute to disease susceptibility, alternatively they may reflect interactions between ALL-associated haplotypes in this region.

  4. Relapsing Polychondritis Following Alopecia Areata

    Directory of Open Access Journals (Sweden)

    John C. Starr

    2010-01-01

    Full Text Available A case of alopecia areata followed by relapsing polychondritis is presented. Similar cases from the literature are reviewed and speculation about the relationship of these diseases is offered. Although the occurrence of these diseases together could be coincidental, an association seems immunologically plausible. Thus, relapsing polychondritis might be an unusual systemic manifestation of alopecia areata.

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

    OpenAIRE

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

    2013-01-01

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

  6. Clinical characteristics and genetic analysis of childhood acute lymphoblastic leukemia with hemophagocytic lymphohistiocytosis: a Japanese retrospective study by the Kyushu-Yamaguchi Children's Cancer Study Group.

    Science.gov (United States)

    Moritake, Hiroshi; Kamimura, Sachiyo; Nunoi, Hiroyuki; Nakayama, Hideki; Suminoe, Aiko; Inada, Hiroko; Inagaki, Jiro; Yanai, Fumio; Okamoto, Yasuhiro; Shinkoda, Yuichi; Shimomura, Maiko; Itonaga, Nobuyoshi; Hotta, Noriko; Hidaka, Yasufumi; Ohara, Osamu; Yanagimachi, Masakatsu; Nakajima, Noriko; Okamura, Jun; Kawano, Yoshifumi

    2014-07-01

    This present study sought to analyze acute lymphoblastic leukemia (ALL) patients with hemophagocytic lymphohistiocytosis (HLH) registered in Kyushu-Yamaguchi Children's Cancer Study Group studies conducted between 1996 and 2007. Four of 357 patients, including two of 318 patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL) and two of 39 of those with T cell acute lymphoblastic leukemia (T-ALL), were identified. HLH was observed more frequently in the T-ALL patients than in the BCP-ALL patients (P = 0.061). The mean age of 13.0 years at the diagnosis of leukemia in the HLH + ALL group was significantly higher than the 6.05 years observed in the remaining ALL groups (P = 0.001). A female predisposition was noted, as all four patients were female (P = 0.043). In two of four patients, the leukemic cells exhibited deletions on the long arm of chromosome 6 (P = 0.003). Three patients suffered from HLH during maintenance therapy. Parvovirus B19 infection and cytomegalovirus reactivation were identified as causes of HLH in one and two patients, respectively. All four patients are currently in complete remission, although one developed relapse of leukemia after receiving maintenance therapy. Based on the genetic analyses, non-synonymous single nucleotide polymorphisms (SNPs) in UNC13D, syntaxin 11, and STXBP2 were identified in all patients. Clinicians should therefore be aware of the risk of HLH during maintenance therapy, especially in older T-ALL patients with SNPs in familial HLH causative genes.

  7. Cured meat, vegetables, and bean-curd foods in relation to childhood acute leukemia risk: a population based case-control study.

    Science.gov (United States)

    Liu, Chen-Yu; Hsu, Yi-Hsiang; Wu, Ming-Tsang; Pan, Pi-Chen; Ho, Chi-Kung; Su, Li; Xu, Xin; Li, Yi; Christiani, David C

    2009-01-13

    Consumption of cured/smoked meat and fish leads to the formation of carcinogenic N-nitroso compounds in the acidic stomach. This study investigated whether consumed cured/smoked meat and fish, the major dietary resource for exposure to nitrites and nitrosamines, is associated with childhood acute leukemia. A population-based case-control study of Han Chinese between 2 and 20 years old was conducted in southern Taiwan. 145 acute leukemia cases and 370 age- and sex-matched controls were recruited between 1997 and 2005. Dietary data were obtained from a questionnaire. Multiple logistic regression models were used in data analyses. Consumption of cured/smoked meat and fish more than once a week was associated with an increased risk of acute leukemia (OR = 1.74; 95% CI: 1.15-2.64). Conversely, higher intake of vegetables (OR = 0.55; 95% CI: 0.37-0.83) and bean-curd (OR = 0.55; 95% CI: 0.34-0.89) was associated with a reduced risk. No statistically significant association was observed between leukemia risk and the consumption of pickled vegetables, fruits, and tea. Dietary exposure to cured/smoked meat and fish may be associated with leukemia risk through their contents of nitrites and nitrosamines among children and adolescents, and intake of vegetables and soy-bean curd may be protective.

  8. Relapsing Painful Ophthalmoplegic Neuropathy: No longer a "Migraine," but Still a Headache.

    Science.gov (United States)

    Smith, Stacy V; Schuster, Nathaniel M

    2018-06-14

    Recurrent painful ophthalmoplegic neuropathy (RPON), formerly known as ophthalmoplegic migraine, is an uncommon disorder with repeated episodes of ocular cranial nerve neuropathy associated with ipsilateral headache. This review discusses the clinical presentation, current understanding of the pathophysiology, key differential diagnoses, and evaluation and treatment of RPON. The literature is limited due to the rarity of the disorder. Recent case reports and series continue to suggest the age of first attack is most often during childhood or adolescence as well as a female predominance. Multiple recent case reports and series demonstrate focal enhancement of the affected cranial nerve, as the nerve root exits the brainstem. This finding contributed to the current classification of the disorder as a neuropathy, with the present understanding that it is due to a relapsing-remitting inflammatory or demyelinating process. The link to migraine remains a cause of disagreement in the literature. RPON is a complex disorder with features of inflammatory neuropathy and an unclear association with migraine. Regardless, the overall prognosis is good for individual episodes, but permanent nerve damage may accumulate with repeated attacks. A better understanding of the pathogenesis is needed to clarify whether it truly represents a single disorder and to guide its treatment. Until that time, a combined approach with acute and preventive therapies can mitigate acute symptoms as well as attempt to limit recurrence of this disabling syndrome.

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

    Directory of Open Access Journals (Sweden)

    Nahid Reisi

    2015-01-01

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

  10. The Rotter I-E scale as a predictor of relapse in a population of compulsive gamblers.

    Science.gov (United States)

    Johnson, E E; Nora, R M; Bustos, N

    1992-06-01

    Profile surveys, completed Rotter I-E scales, and questionnaires on past relapse behavior were collected from 108 New Jersey compulsive gamblers who attended Gamblers Anonymous, and an attempt was made, based on the findings, to predict incidence of compulsive gamblers' relapse. Relationships between I-E scores and extent of relapse-free periods, and I-E scores and relapse, with the variables of religious background, age, marital status, education, type of work, and childhood physical abuse were investigated. In every instance the relationship found was statistically non-significant.

  11. Consequenses of childhood adversity on health concerns in adulthood

    African Journals Online (AJOL)

    Consequenses of childhood adversity on health concerns in adulthood. ... childhood adversity have similar levels of depression, acute and chronic health. ... to explain the pathways linking childhood adversity to physical health in adulthood.

  12. The association of reduced folate carrier 80G>A polymorphism to outcome in childhood acute lymphoblastic leukemia interacts with chromosome 21 copy number

    DEFF Research Database (Denmark)

    Gregers, Jannie; Christensen, Ib Jarle; Dalhoff, Kim

    2010-01-01

    with chromosome 21 copy number in the leukemic clone. A total of 500 children with acute lymphoblastic leukemia treated according to the common Nordic treatment protocols were included, and we found that the RFC AA variant was associated with a 50% better chance of staying in remission compared with GG or GA......The reduced folate carrier (RFC) is involved in the transport of methotrexate (MTX) across the cell membrane. The RFC gene (SLC19A1) is located on chromosome 21, and we hypothesized that the RFC80 G>A polymorphism would affect outcome and toxicity in childhood leukemia and that this could interact...... variants (P = .046). Increased copy numbers of chromosome 21 appear to improve outcome also in children with GA or GG variant. In a subset of 182 children receiving 608 high-dose MTX courses, we observed higher degree of bone marrow toxicity in patients with the RFC AA variant compared with GA/GG variants...

  13. Family-based exome-wide association study of childhood acute lymphoblastic leukemia among Hispanics confirms role of ARID5B in susceptibility.

    Directory of Open Access Journals (Sweden)

    Natalie P Archer

    Full Text Available We conducted an exome-wide association study of childhood acute lymphoblastic leukemia (ALL among Hispanics to confirm and identify novel variants associated with disease risk in this population. We used a case-parent trio study design; unlike more commonly used case-control studies, this study design is ideal for avoiding issues with population stratification bias among this at-risk ethnic group. Using 710 individuals from 323 Guatemalan and US Hispanic families, two inherited SNPs in ARID5B reached genome-wide level significance: rs10821936, RR = 2.31, 95% CI = 1.70-3.14, p = 1.7×10-8 and rs7089424, RR = 2.22, 95% CI = 1.64-3.01, p = 5.2×10-8. Similar results were observed when restricting our analyses to those with the B-ALL subtype: ARID5B rs10821936 RR = 2.22, 95% CI = 1.63-3.02, p = 9.63×10-8 and ARID5B rs7089424 RR = 2.13, 95% CI = 1.57-2.88, p = 2.81×10-7. Notably, effect sizes observed for rs7089424 and rs10821936 in our study were >20% higher than those reported among non-Hispanic white populations in previous genetic association studies. Our results confirmed the role of ARID5B in childhood ALL susceptibility among Hispanics; however, our assessment did not reveal any strong novel inherited genetic risks for acute lymphoblastic leukemia among this ethnic group.

  14. Family-based exome-wide association study of childhood acute lymphoblastic leukemia among Hispanics confirms role of ARID5B in susceptibility

    Science.gov (United States)

    Stoltze, Ulrik; Scheurer, Michael E.; Wilkinson, Anna V.; Lin, Ting-Nien; Qian, Maoxiang; Goodings, Charnise; Swartz, Michael D.; Ranjit, Nalini; Rabin, Karen R.; Peckham-Gregory, Erin C.; Plon, Sharon E.; de Alarcon, Pedro A.; Zabriskie, Ryan C.; Antillon-Klussmann, Federico; Najera, Cesar R.; Yang, Jun J.

    2017-01-01

    We conducted an exome-wide association study of childhood acute lymphoblastic leukemia (ALL) among Hispanics to confirm and identify novel variants associated with disease risk in this population. We used a case-parent trio study design; unlike more commonly used case-control studies, this study design is ideal for avoiding issues with population stratification bias among this at-risk ethnic group. Using 710 individuals from 323 Guatemalan and US Hispanic families, two inherited SNPs in ARID5B reached genome-wide level significance: rs10821936, RR = 2.31, 95% CI = 1.70–3.14, p = 1.7×10−8 and rs7089424, RR = 2.22, 95% CI = 1.64–3.01, p = 5.2×10−8. Similar results were observed when restricting our analyses to those with the B-ALL subtype: ARID5B rs10821936 RR = 2.22, 95% CI = 1.63–3.02, p = 9.63×10−8 and ARID5B rs7089424 RR = 2.13, 95% CI = 1.57–2.88, p = 2.81×10−7. Notably, effect sizes observed for rs7089424 and rs10821936 in our study were >20% higher than those reported among non-Hispanic white populations in previous genetic association studies. Our results confirmed the role of ARID5B in childhood ALL susceptibility among Hispanics; however, our assessment did not reveal any strong novel inherited genetic risks for acute lymphoblastic leukemia among this ethnic group. PMID:28817678

  15. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... in RRMS; however, each person's experience with RRMS will be unique. Following a relapse, the new symptoms ... and worsening, you and your MS care provider will likely want to consider a more aggressive treatment ...

  16. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... course – is characterized by clearly defined attacks of new or increasing neurologic symptoms. These attacks – also called ... either active (with relapses and/or evidence of new MRI activity) or not active , as well as ...

  17. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... defined attacks of new or increasing neurologic symptoms. These attacks – also called relapses or exacerbations – are followed ... as well as the nerve fibers themselves. During these inflammatory attacks, activated immune cells cause small, localized ...

  18. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Treating MS Comprehensive Care Find an MS Care Provider Medications Managing Relapses Rehabilitation Complementary & Alternative Medicines For Clinicians Resources & Support Library & Education Programs Find Support Advanced Care ...

  19. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... without symptoms of which the person is aware. What happens in RRMS? Relapsing-remitting MS is defined ... a different mechanism of action in order to control the disease activity more effectively and help prevent ...

  20. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Rule Out For Clinicians Treating MS Comprehensive Care Find an MS Care Provider Medications Managing Relapses Rehabilitation ... Medicines For Clinicians Resources & Support Library & Education Programs Find Support Advanced Care Needs Resources for Specific Populations ...

  1. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... the periods of remission. At different points in time, RRMS can be further characterized as either active ( ... increase in disability over a specified period of time following a relapse) or not worsening . An increase ...

  2. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... attacks of inflammation (relapses) in the CNS, progressive forms of MS involve much less of this type ... and memory or information processing). People with progressive forms of MS are more likely to experience gradually ...

  3. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Team Make the Most of Your Doctor Visits Advance Medical Directives d Find an MS Care Provider ... in RRMS; however, each person's experience with RRMS will be unique. Following a relapse, the new symptoms ...

  4. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... as shown by the arrows, often occur as part of a relapse. However, new MRI lesions indicating ... course of your disease at different points in time helps you and your MS care provider discuss ...

  5. 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...

  6. Tumour genesis syndrome: severe hypophosphatemia and hypokalemia may be ominous presenting findings in childhood acute myeloid leukaemia.

    Science.gov (United States)

    Chan, Winnie Ky; Chang, Kai On; Lau, Wing Hung

    2017-08-01

    We report a 16-year-old girl who was diagnosed with acute leukaemia and a marked leucocytosis >200 × 10 9 /L. She presented with marked hypophosphatemia, hypokalemia, acute renal failure and acute respiratory failure. These electrolytes disturbances may indicate rapid tumour genesis. These ominous findings required urgent treatment to halt the crises of rapid leukemic cell proliferation. Mark hypophosphatemia and hypokalemia may be presenting electrolyte abnormalities in a patient with acute leukaemia, and these may be indicators of aggressive tumour genesis. What is known: • Mild electrolyte disturbances are common in oncology patients • Tumour lysis syndrome is well recognized by paediatriaticians What is new: • Life-threatening hypophosphatemia is an uncommon presentation • These electrolytes disorders may indicate an aggressive tumour genesis process even at presentation and require urgent treatment.

  7. Acute Transverse Myelitis in Children, Literature Review.

    Science.gov (United States)

    Tavasoli, Azita; Tabrizi, Aidin

    2018-01-01

    Acute transverse myelitis (ATM) is a rare inflammatory demyelinating disorder characterized by relatively acute onset of motor, sensory, and autonomic dysfunction. Children comprise 20% of total cases of ATM. In this review, we described the current literature on childhood ATM, focusing on the epidemiology, pathogenesis, clinical presentation, approach to diagnosis, differential diagnosis, treatment and outcome in the pediatric population. We searched the related articles in electronic databases such as Scopus, EMBASE, Google Scholar, and PubMed. All study designs were included and the essential key words for searching were myelitis, acute transverse myelitis, childhood transverse myelitis, and acquired demyelinating syndromes. The related data focusing on the epidemiology, pathogenesis, clinical presentation, diagnostic approach and differential diagnosis, treatment and outcome of pediatric ATM were gathered and described. ATM is a heterogeneous disorder in children with a broad spectrum of clinical presentation, etiology, and outcome. It may be the first presentation of relapsing acquired demyelinating syndromes and also must be distinguished from compressive and noninflamatory myelopathies. Correct diagnosis is crucial for treatment and prognosis.

  8. Acute form of multiple sclerosis in a child simulation encephalitis

    International Nuclear Information System (INIS)

    Niagolova, S.; Karapasheva, V.; Nikolova, M.

    2007-01-01

    Multiple sclerosis (MS) is considered the most common demyelinating process involving the CNS. Although usually considered an adult disease multiple sclerosis can begin to manifest during childhood. The clinical presentation of the disease in early childhood can range from paraesthesias to dramatic presentations, suggesting diffuse encephalopathy with cerebral oedema, meningismus and impaired consciousness. Multiple sclerosis is usually characterized by a typical relapsing-remitting clinical course. But there are acute, clinically fulminant forms with atypical. neurologic symptoms and death in months. MRI has become increasingly relevant in the diagnosis of multiple sclerosis in the past years. Yet, the specificity is limited. Atypical forms of MS and other diseases of CNS may show similar patterns on MRI. We report a case of 7 years old boy with clinically fulminant Marburg type of multiple sclerosis that ended with death in two months. The patient was a diagnostic problem despite the certain degree of clinical and radiological suspicion. The postmortem diagnosis is based on pathomorphologic changes (gross pathologic and microscopic features) in CNS.The present case is of clinical, radiological and pathomorphologic interest because of its early onset in childhood, unusual clinical course and acute progression. Awareness of the MRI features of multiple sclerosis and MS-variants (subtypes) may help in such atypical presentations in childhood. (authors)

  9. Childhood psoriasis

    Directory of Open Access Journals (Sweden)

    Dogra Sunil

    2010-01-01

    Full Text Available Psoriasis is a common dermatosis in children with about one third of all patients having onset of disease in the first or second decade of life. A chronic disfiguring skin disease, such as psoriasis, in childhood is likely to have profound emotional and psychological effects, and hence requires special attention. Psoriasis in children has been reported to differ from that among adults being more frequently pruritic; plaque lesions are relatively thinner, softer, and less scaly; face and flexural involvement is common and guttate type is the characteristic presentation. Whether onset in childhood predicts a more severe form of psoriasis is a matter of controversy, it may cause significant morbidity particularly if it keeps relapsing. Most children have mild form of psoriasis which can be generally treated effectively with topical agents such as emollients, coal tar, corticosteroids, dithranol, calcipotriol etc. according to age and the sites affected. Narrow band UVB is the preferred form of phototherapy in children for moderate to severe disease or in patients not responding to topical therapy alone. Systemic therapies are reserved for more severe and extensive cases that cannot be controlled with topical treatment and/or phototherapy such as severe plaque type, unstable forms like erythrodermic and generalized pustular psoriasis and psoriatic arthritis. There are no controlled trials of systemic therapies in this age group, most experience being with retinoids and methotrexate with favorable results. Cyclosporine can be used as a short-term intermittent crisis management drug. There is an early promising experience with the use of biologics (etanercept and infliximab in childhood psoriasis. Systemic treatments as well as phototherapy have limited use in children due to cumulative dose effects of drugs, low acceptance, and risk of gonadal toxicity. More evidence-based data is needed about the effectiveness and long-term safety of topical

  10. Early lymphocyte recovery as a predictor of outcome, including relapse, after hematopoieticstem cell transplantation

    Directory of Open Access Journals (Sweden)

    Juliane Morando

    2012-01-01

    Full Text Available BACKGROUND: Despite advances in the treatment of acute leukemia, many patients need to undergo hematopoietic stem cell transplantation. Recent studies show that early lymphocyte recovery may be a predictor of relapse and survival in these patients. OBJECTIVE: To analyze the influence of lymphocyte recovery on Days +30 and +100 post-transplant on the occurrence of relapse and survival. METHODS: A descriptive, retrospective study was performed of 137 under 21-year-old patients who were submitted to hematopoietic stem cell transplantation for acute leukemia between 1995 and 2008. A lymphocyte count 0.3 x 10(9/L were considered adequate. Lymphocyte recovery was also analyzed on Day +100 with < 0.75 x 10(9/Land < 0.75 x 10(9/L being considered inadequate and adequate lymphocyte recovery, respectively. RESULTS: There was no significant difference in the occurrence of relapse between patients with inadequate and adequate lymphocyte recovery on Day +30 post-transplant. However, the transplant-related mortality was significantly higher in patients with inadequate recovery on Day +30. Patients with inadequate lymphocyte recovery on Day +30 had worse overall survival and relapse-free survival than patients with adequate recovery. There was no significant difference in the occurrence of infections and acute or chronic graft-versus-host disease. Patients with inadequate lymphocyte recovery on Day +100 had worse overall survival and relapse-free survival and a higher cumulative incidence of relapse. CONCLUSION: The evaluation of lymphocyte recovery on Day +30 is not a good predictor of relapse after transplant however patients with inadequate lymphocyte recovery had worse overall survival and relapse-free survival. Inadequate lymphocyte recovery on Day +100 is correlated with higher cumulative relapse as well as lower overall survival and relapse-free survival.

  11. New immunotherapy approach leads to remission in patients with the most common type of childhood cancer | Center for Cancer Research

    Science.gov (United States)

    Chimeric antigen receptor (CAR) T-cell immunotherapy has emerged as a promising treatment for pre-B cell acute lymphoblastic leukemia (B-ALL), the most common type of childhood cancer. B-ALL is characterized by an overproduction of immature white blood cells called lymphoblasts. In a trial led by Center for Cancer Research investigators, around 70 to 90 percent of patients whose B-ALL has relapsed or developed resistance to chemotherapy entered remission after CAR T-cell therapy targeting CD19. Read more…

  12. Use of G-CSF to hasten neutrophil recovery after auto-SCT for AML is not associated with increased relapse incidence: a report from the Acute Leukemia Working Party of the EBMT.

    Science.gov (United States)

    Czerw, T; Labopin, M; Gorin, N-C; Giebel, S; Blaise, D; Dumas, P-Y; Foa, R; Attal, M; Schaap, N; Michallet, M; Bonmati, C; Veelken, H; Mohty, M

    2014-07-01

    Application of G-CSF in AML is controversial as leukemic blasts may express receptors interacting with the cytokine, which may stimulate leukemia growth. We retrospectively analyzed the impact of G-CSF use to accelerate neutrophil recovery after auto-SCT on outcome. Adults with AML in first CR autografted between 1994 and 2010 were included. Nine hundred and seventy two patients were treated with G-CSF after auto-SCT whereas 1121 were not. BM and PB were used as a source of stem cells in 454 (22%) and 1639 (78%) cases, respectively. The incidence of relapse at 5 years in the BM-auto-SCT group was 38% for patients receiving post-transplant G-CSF and 43% for those not treated with G-CSF, P=0.46. In the PB-auto-SCT cohort, respective probabilities were 48% and 49%, P=0.49. No impact of the use of G-CSF could be demonstrated with respect to the probability of leukemia-free survival: in the BM-auto-SCT group, 51% for G-CSF(+) and 48% for G-CSF(-), P=0.73; in PB-auto-SCT group, 42% for G-CSF(+) and 43% for G-CSF(-), P=0.83. Although G-CSF administration significantly shortened the neutropenic phase, no beneficial effect was observed with regard to non-relapse mortality. In patients with AML, the use of G-CSF after auto-SCT is not associated with increased risk of relapse irrespective of the source of stem cells used.

  13. Clinical trials of CCLSG L874 and I874 protocols without cranial irradiation for standard-risk acute lymphoblastic leukemia in childhood

    International Nuclear Information System (INIS)

    Koizumi, Shoichi; Fujimoto, Takeo; Tsurusawa, Masahito

    1992-01-01

    In the CCLSG-874 protocol for children with low-risk (LR) and intermediate-risk (IR) acute lymphoblastic leukemia (ALL), two regimens with or without cranial irradiation (CI) were compared with respect to their ability to prevent central nervous system (CNS) leukemia and to improve overall outcome of ALL. From 1987 to 1990, 82 and 109 evaluable patients were registered into L874 and I874 protocols for LR and IR patients, respectively. All responders to induction therapy were randomized to treatment with 18 Gy of CI plus intrathecal methotrexate (MTX it) or to treatment with high-dose MTX plus MTX it. Patients were then treated with standard maintenance regimens of L874 and I874. At a median follow-up of 39 months (range 14-58 months) there was no difference in the rate of hematologic relapse between the CI group and MTX group. The rate of CNS relapse in the MTX group seemed to be higher (3 of 39 in L874 and 2 of 54 in I874) than that in the CI group (1 of 43 in L874 and 0 of 55 in I874), but these data were not statistically significant. The rates of 4-year event-free survival (EFS) in L874 were 81.1±7.6% (mean±SE) and 75.2±7.9% (ns) for the CI and MTX group, respectively, and the rates of EFS in I874 were 70.0±13.6% and 70.0±9.0% (ns) for the CI and MTX group, respectively. These data suggest that MTX alone may be as effective as CI to prolong disease-free survival in LR and IR ALL although further continuous studies are needed. Analysis of serial CCLSG protocols for ALL from 1981 revealed that the rate of EFS of ALL allover including all risk groups has gradually been increasing from 44.2±3.6% for 811 protocol and 53.1±3.5% for 841 to 65.5±3.6% for the present 874 protocol. (author)

  14. White versus gray matter function as seen on neuropsychological testing following bone marrow transplant for acute leukemia in childhood

    Directory of Open Access Journals (Sweden)

    Fiona S Anderson

    2008-03-01

    Full Text Available Fiona S Anderson1, Alicia S Kunin-Batson1, Joanna L Perkins2, K Scott Baker31Divisions of Pediatric Clinical Neuroscience; 2Department of Pediatric Hematology/Oncology, Children’s Hospitals and Clinics, Minneapolis, MN, USA and 3Hematology/Oncology/BMT, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USAAbstract: Current theory suggests that neurocognitive late effects of treatments for childhood cancer such as difficulties with attention, processing speed and visual-motor ability are the result of white matter damage. Neuroimaging studies have produced a variety of white matter findings. However, although white matter is thought to be differentially affected, previous studies have not demonstrated a discrepancy between white and gray matter function. The present study included 36 children treated for childhood leukemia with hematopoietic stem cell transplant (HCT. Their performance on neurocognitive measures traditionally thought to measure white matter was compared to performance on measures thought to measure gray matter function. Composite white and gray matter standard scores were created based on neuropsychological measures that individuals with known white or gray matter damage perform poorly. As predicted, composite white matter scores (mean = 98.1 were significantly lower (t = 2.26, p = 0.03 than composite gray matter scores (mean = 102.5. Additionally, as gray matter performance increased, the difference between gray and white matter scores increased (R = 0.353, p = 0.035. Overall, the results of this study support the current theory that white matter damage is responsible for the more subtle neurocognitive late effects resulting from treatment for childhood leukemia.Keywords: late effects of cancer treatment, leukemia, neuropsychology, white matter, brain function

  15. Cost-effective multiplexing before capture allows screening of 25 000 clinically relevant SNPs in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Wesolowska, Agata; Dalgaard, M. D.; Borst, L.

    2011-01-01

    designed a cost-effective, high-throughput capture assay of â¼25â000 clinically relevant SNPs, and demonstrated that multiple samples can be tagged and pooled before genome capture in targeted enrichment with a sufficient sequencing depth for genotyping. This multiplexed, targeted sequencing method allows...... exploration of the impact of pharmacogenetics on efficacy and toxicity in childhood ALL treatment, which will be of importance for personalized chemotherapy.Leukemia advance online publication, 18 March 2011; doi:10.1038/leu.2011.32....

  16. Relapse prevention and smoking cessation.

    Science.gov (United States)

    Davis, J R; Glaros, A G

    1986-01-01

    A multicomponent smoking relapse prevention treatment based on Marlatt and Gordon's (1980) model of the relapse process was developed and evaluated. Behavior-analytic methods were used to develop assessment instruments, training situations, and coping responses. The prevention components were presented in the context of a basic broad-spectrum stop-smoking program, and were compared with the basic program plus discussion control, and the basic program alone. Smoking-related dependent variables generally did not differ between groups at any time from pre-treatment to 12 month follow-up. Only the subjects in the relapse prevention condition improved problem-solving and social skills needed to cope with high-risk situations. These subjects also tended to take longer to relapse and smoke fewer cigarettes at the time of relapse. Subjects above the median level of competence on measures of social skill at post-treatment remained abstinent significantly longer. Maintenance of non-smoking was found to be related to the degree of competence with which individuals deal with high-risk situations. Results are discussed in relation to models of compliance with therapeutic regimens.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  20. 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...

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

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

  3. 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

  4. A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study

    NARCIS (Netherlands)

    M.L. den Boer (Monique); M.A. van Slegtenhorst (Marjon); R.X. de Menezes (Renee); M.H. Cheok (Meyling); J.G.C.A.M. Buijs-Gladdines (Jessica); S.T.C.J.M. Arentsen-Peters (Susan); L.J.C.M. van Zutven (Laura); H.B. Beverloo (Berna); P.J. van der Spek (Peter); G. Escherich (Gabriele); M.A. Horstmann (Martin); G.E. Janka-Schaub (Gritta); W.A. Kamps (Willem); W.E. Evans (William); R. Pieters (Rob)

    2009-01-01

    textabstractBackground: Genetic subtypes of acute lymphoblastic leukaemia (ALL) are used to determine risk and treatment in children. 25% of precursor B-ALL cases are genetically unclassified and have intermediate prognosis. We aimed to use a genome-wide study to improve prognostic classification of

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

    NARCIS (Netherlands)

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

  6. 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.

  7. An intronic polymorphism of IRF4 gene influences gene transcription in vitro and shows a risk association with childhood acute lymphoblastic leukemia in males.

    Science.gov (United States)

    Do, Thuy N; Ucisik-Akkaya, Esma; Davis, Charronne F; Morrison, Brittany A; Dorak, M Tevfik

    2010-02-01

    The interferon regulatory factor (IRF) family of DNA-binding proteins regulates expression of interferon-inducible genes with roles in the immune response and carcinogenesis. IRF4 is involved in the differentiation of B and T cells and is overexpressed in B-cell malignancies as a result of c-REL (NF-kappaB) hyperactivation. IRF4 polymorphisms are associated with susceptibility to chronic lymphoid leukemia (CLL) and non-Hodgkin lymphoma (NHL). We examined 13 IRF4 SNPs in 114 cases of childhood acute lymphoblastic leukemia (ALL) and 388 newborn controls from Wales (U.K.) using TaqMan assays. IRF4 intron 4 SNP rs12203592 showed a male-specific risk association (OR=4.4, 95% CI=1.5 to 12.6, P=0.007). Functional consequences of the C>T substitution at this SNP were assessed by cell-based reporter assays using three different cell lines. We found a repressive effect of the rs12203592 wildtype allele C on IRF4 promoter activity (Pcell line tested. Thus, homozygosity for the rs12203592 variant allele would result in increased IRF4 expression. This increase would be compounded by high levels of NF-kappaB activity in males due to the absence of estrogen. IRF4 differs from other IRFs in its anti-interferon activity which interferes with immune surveillance. We propose that a detailed study of IRF4 can provide information on the mechanism of the sex effect and the role of immune surveillance in childhood ALL development. Copyright 2009 Elsevier B.V. All rights reserved.

  8. 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....... Improvements in systemic and intrathecal chemotherapy have reduced the use of central nervous system (CNS) irradiation to...

  9. Family-based exome-wide assessment of maternal genetic effects on susceptibility to childhood B-cell acute lymphoblastic leukemia in Hispanics

    Science.gov (United States)

    Archer, Natalie P.; Perez-Andreu, Virginia; Scheurer, Michael E.; Rabin, Karen R.; Peckham-Gregory, Erin C.; Plon, Sharon E.; Zabriskie, Ryan C.; De Alarcon, Pedro A.; Fernandez, Karen S.; Najera, Cesar R.; Yang, Jun J.; Antillon-Klussmann, Federico; Lupo, Philip J.

    2016-01-01

    Background Children of Hispanic ancestry have a higher incidence of acute lymphoblastic leukemia (ALL) than other ethnic groups, but the genetic basis for racial disparities remain incompletely understood. Genome-wide association studies (GWAS) of childhood ALL to date have focused on inherited genetic effects; however, maternal genetic effects (the role of maternal genotype on offspring phenotype development) may also play a role in ALL susceptibility. Methods We conducted a family-based exome-wide association study (EXWAS) of maternal genetic effects among Hispanics with childhood B-cell ALL (B-ALL) using the Illumina Human Exome BeadChip. We used a discovery cohort of 312 Guatemalan and Hispanic American families and an independent replication cohort of 152 Hispanic American families. Results Three maternal SNPs approached our threshold for significance, after correction for multiple testing (P<1.0×10−6): MTL5 rs12365708 (RR=2.62, 95% CI=1.61-4.27, P=1.8×10−5); ALKBH1 rs6494 (RR=3.77, 95% CI=1.84-7.74, P=3.7×10−5); NEUROG3 rs4536103 (RR=1.75, 95% CI=1.30-2.37, P=1.2×10−4). While effect sizes were similar, these SNPs were not nominally significant in our replication cohort. In a meta-analysis comprised of the discovery cohort and the replication cohort, these SNPs were still not statistically significant after correction for multiple comparisons (rs12365708: pooled RR=2.27, 95% CI=1.48-3.50, P=1.99×10−4; rs6494: pooled RR=2.31, 95% CI=1.38-3.85, P=0.001; rs4536103: pooled RR=1.67, 95% CI=1.29-2.16, P=9.23×10−5). Conclusions In the first family-based EXWAS to investigate maternal genotype effects associated with childhood ALL, our results did not implicate a strong role of maternal genotype on disease risk among Hispanics; however, we identified three maternal SNPs that may play a modest role in susceptibility. PMID:27529658

  10. Potential gonadotoxicity of treatment in relation to quality of life and mental well-being of male survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Gunn, Mirja Erika; Lähteenmäki, Päivi Maria; Puukko-Viertomies, Leena-Riitta; Henriksson, Markus; Heikkinen, Risto; Jahnukainen, Kirsi

    2013-09-01

    Results of earlier studies concerning quality of life (QOL) and psychosocial coping of childhood acute lymphoblastic leukemia (ALL) survivors have been inconsistent. Some treatments for ALL affect testicular function and we hypothesized that this may influence the QOL and psychosocial coping of male survivors. Our aims were to assess the QOL and psychosocial coping of male long-term ALL survivors and to evaluate the effect of both testosterone level and the potential gonadotoxicity of various treatment modalities on them. Fifty-two male long-term survivors treated for childhood ALL at Helsinki University Hospital between 1970 and 1995, and 56 age- and gender-matched controls were studied. The participants completed a self-report questionnaire including questions on sociodemographics, RAND-36 to assess QOL, General Health Questionnaire and Beck Depression Inventory to assess mental well-being, and CAGE to assess alcohol abuse/dependence. Testosterone levels were measured, and treatment details were reviewed. ALL survivors in general had QOL close to that of controls or population norms. Decreased QOL was seen in physical health-related subscales, and vitality and emotional well-being were lowered in survivors with more gonadotoxic treatment modalities. No single independent factor in the treatment or the level of testosterone could, however, be found to clearly explain the variation in QOL scores of the survivors. Mental well-being of most of the survivors was good, but a subgroup with previous cyclophosphamide treatment or testicular irradiation showed increased risk of psychiatric morbidity. The male ALL survivors generally cope well, but increased focus on specific risk groups seems to be necessary. Further studies using patient interviews would probably point out issues concerning the QOL and psychosocial coping of ALL survivors, which may not emerge in these screening studies. In general, more attention should be paid for physical functioning of childhood ALL

  11. Whole-exome sequencing of a rare case of familial childhood acute lymphoblastic leukemia reveals putative predisposing mutations in Fanconi anemia genes.

    Science.gov (United States)

    Spinella, Jean-François; Healy, Jasmine; Saillour, Virginie; Richer, Chantal; Cassart, Pauline; Ouimet, Manon; Sinnett, Daniel

    2015-07-23

    Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. While the multi-step model of pediatric leukemogenesis suggests interplay between constitutional and somatic genomes, the role of inherited genetic variability remains largely undescribed. Nonsyndromic familial ALL, although extremely rare, provides the ideal setting to study inherited contributions to ALL. Toward this goal, we sequenced the exomes of a childhood ALL family consisting of mother, father and two non-twinned siblings diagnosed with concordant pre-B hyperdiploid ALL and previously shown to have inherited a rare form of PRDM9, a histone H3 methyltransferase involved in crossing-over at recombination hotspots and Holliday junctions. We postulated that inheritance of additional rare disadvantaging variants in predisposing cancer genes could affect genomic stability and lead to increased risk of hyperdiploid ALL within this family. Whole exomes were captured using Agilent's SureSelect kit and sequenced on the Life Technologies SOLiD System. We applied a data reduction strategy to identify candidate variants shared by both affected siblings. Under a recessive disease model, we focused on rare non-synonymous or frame-shift variants in leukemia predisposing pathways. Though the family was nonsyndromic, we identified a combination of rare variants in Fanconi anemia (FA) genes FANCP/SLX4 (compound heterozygote - rs137976282/rs79842542) and FANCA (rs61753269) and a rare homozygous variant in the Holliday junction resolvase GEN1 (rs16981869). These variants, predicted to affect protein function, were previously identified in familial breast cancer cases. Based on our in-house database of 369 childhood ALL exomes, the sibs were the only patients to carry this particularly rare combination and only a single hyperdiploid patient was heterozygote at both FANCP/SLX4 positions, while no FANCA variant allele carriers were identified. FANCA is the most commonly mutated gene in FA and is essential for

  12. The Role of Type I Insulin Like Growth Factor Receptor (IGF-IR) in Adult and Childhood Acute Lymphoblastic Leukemia

    International Nuclear Information System (INIS)

    KAMEL, M.M.; HAMMAM, A.A.; ELHOSEINY, Sh.M.; MOKHLES, A.; MOHSEN, E.

    2008-01-01

    Background: Type 1 insulin like growth factor receptor (IGF-IR) is over expressed in many tumors including hematological cancers. It is a critical signaling molecule for tumor cell proliferation and survival. Data suggest that IGF-IR antibodies can effectively and specifically inhibit cancer cell growth in vitro and in vivo. Blockage of IGF-IR expression could be a promising therapeutic approach for the management of cancer patients. Aim of Work: To characterize the expression pattern of IGF-IR gene in malignant lymphoblasts of children and adults suffering from ALL in relation to clinical features at diagnosis. Patients and Methods: The expression of IGF-IR was analyzed in 60 patients with ALL, 30 childhood ALL (16 newly diagnosed and 14 in complete remission) and 30 adulthood ALL (15 newly diagnosed and 15 in complete remission) together with 20 normal age and sex matched healthy controls using a Real-Time Quantitative Reverse- Transcriptase Polymerase Chain Reaction (RTQ-PCR) to assess the possible relation, association or correlation between IGF-IR expression and ALL clinical and laboratory features at diagnosis. Results: IGF-IR was expressed in all 60 patients with ALL; the expression levels of IGF-IR were significantly higher in newly diagnosed patients than in patients in complete remission (CR) and controls (p<0.001). There were no statistically significant differences in the expression of IGF-IR between patients with different clinical and laboratory features. Conclusion: IGF-1R seems to play a crucial role in patients with ALL since it is expressed in all ALL cases (adulthood and childhood). Therefore, new therapeutic agents targeting IGF-1R may provide a better chance for those patients

  13. Clinical Trials and Tribulations: Lessons Learned from Recruiting Pregnant Ex-Smokers for Relapse Prevention

    OpenAIRE

    Lopez, Elena N.; Simmons, Vani Nath; Quinn, Gwendolyn P.; Meade, Cathy D.; Chirikos, Thomas N.; Brandon, Thomas H.

    2008-01-01

    The development of smoking cessation and relapse-prevention interventions for pregnant and postpartum women is a public health priority. However, researchers have consistently reported substantial difficulty in accruing this population into clinical trials. The problem is particularly acute for relapse-prevention studies, which must recruit women who have already quit smoking because of their pregnancy. Although an important target for tobacco control efforts, these individuals represent an e...

  14. Randomized, double-blind clinical trial of a lactose-free and a lactose-containing formula in dietary management of acute childhood diarrhea.

    Science.gov (United States)

    Simakachorn, Nipat; Tongpenyai, Yothi; Tongtan, Orapin; Varavithya, Wandee

    2004-06-01

    Refeeding of artificially fed infants with lactose-containing formula after oral rehydration therapy in the treatment of acute diarrhea was concluded to be indifferent to non-lactose formula by a meta-analysis. In Thai as well as Asian infants and children with low lactase level from genetically determinant and with rotavirus infection, lactose malabsorption is most likely to occur and cause delayed recovery. The aim of this study was to compare the effect of a lactose-free and a lactose-containing formula in dietary management of acute childhood diarrhea. A randomized, double-blind clinical trial of 80 male children, formula-fed, aged 3 to 24 months, admitted with acute watery diarrhea and mild or moderate dehydration, was carried out. All children received oral rehydration therapy for the first 4 hours. After appropriate rehydration, they were fed either a lactose-free formula (Dumex Lactose-Free Formula; treatment group, n = 40) or a lactose-containing formula (Dumex Infant Formula; control group, n = 40) in adjunction with oral rehydration solution. In addition, the infants were fed rice gruel as tolerated. Comparisons of duration of diarrhea, weight gain, vomiting, biochemical changes, stool frequency and weight and unscheduled intravenous fluid were made. Three children (2 treatment, and 1 control) dropped out from the study. The total number of unscheduled intravenous infusions were 6 of 80 children (7.5%), including 2 (5.0%) in the treatment group and 4 (10.0%) in the control group. Three children in the control group did not resolve from diarrhea within 7 days of treatment. Rotavirus was identified in approximately 50% of the children in each group. Using survival analysis, the median duration of diarrhea was significantly shortened by 20.5 hours in the treatment group compared to the control group (77.0 hours in the treatment group vs 97.5 hours in the control group; P = 0.002). Significantly decrease in stool frequency and increase in percent weight gain

  15. Early loss of teeth after treatment for childhood leukemia

    International Nuclear Information System (INIS)

    Herrmann, T.; Doerr, W.; Lesche, A.; Lehmann, D.; Koy, S.

    2004-01-01

    Background: only few reports of effects of radiotherapy in childhood on the dental apparatus are available in the literature. The basis for early loss of teeth appears to be a reduction of the root surface area after radiation exposure. These effects in the periodontium are a consequence of combined radiochemotherapy usually applied for treatment of childhood neoplasia. Chemotherapy alone also results in changes of periodontal development. Case report: a 33-year-old patient is reported, who, at the age of 11 years, received high-dose chemotherapy and radiotherapy of neuroaxis and cranium for acute lymphatic leukemia with relapse. The patient consulted the Implant Section of the Department of Oral and Maxillofacial Surgery because of severe dental changes and tooth loss despite adequate dental care and oral hygiene. Radiation doses given to the superior maxilla and mandible at the age of 11 were estimated to be in the range of 8-25 Gy. Conclusion: intense, life-long dental care and follow-up of patients cured from malignant disease in childhood must hence be postulated in order to minimize dental treatment sequelae by supportive measures, but also to initiate timely adequate dental and prosthetic management. (orig.)

  16. Depression relapse and ethological measures

    NARCIS (Netherlands)

    Hale, WWH; Jansen, JHC; Bouhuys, AL; vandenHoofdakker, RH

    1997-01-01

    Within the framework of interactional theories on depression, the question is raised whether depression relapse can be predicted by observable behavior of remitted patients and their interviewer during an interaction (i.e. discharge interview). Thirty-four patients were interviewed at hospital

  17. Neurocognitive Predictors of Drug Relapse

    NARCIS (Netherlands)

    R. Marhe (Reshmi)

    2013-01-01

    textabstractWorldwide, about 35 million people, that is 0.8% of the world’s adult population, use heroin and/or cocaine and more than 10-13% of these drug users are or will become drug dependent (UNODC, World Drug Report, 2012). Drug dependency is characterized as a chronic relapsing disorder

  18. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Treating MS d Comprehensive Care Developing a Healthcare Team Make the Most of Your Doctor Visits Advance Medical Directives d Find an MS Care Provider Partners in MS Care d Managing Relapses Plasmapheresis d Rehabilitation Functional Electrical Stimulation (FES) ...

  19. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Become an MS Activist Take Action Current Advocacy Issues Advocacy Results Advocacy News d Raise Awareness d ... MS are more likely to experience gradually worsening problems with walking and mobility, along with whatever other symptoms they may have. Diagnosing relapsing-remitting MS (RRMS) Learn More Learn More ... Room MS Prevalence ...

  20. 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

  1. The scars of childhood adversity : Minor stress sensitivity and depressive symptoms in remitted recurrently depressed adult patients

    NARCIS (Netherlands)

    Kok, Gemma; van Rijsbergen, Gerard; Burger, Huibert; Elgersma, Hermien; Riper, Heleen; Cuijpers, Pim; Dekker, Jack; Smit, Filip; Bockting, Claudi

    2014-01-01

    Background: Childhood adversity may lead to depressive relapse through its long-lasting influence on stress sensitivity. In line with the stress sensitization hypothesis, minor (daily) stress is associated with depressive relapse. Therefore, we examine the impact of childhood adversity on daily

  2. Sequential Oral Hydroxyurea and Intravenous Cytosine Arabinoside in Refractory Childhood Acute Leukemia: A Pediatric Oncology Group Phase I Study

    OpenAIRE

    Dubowy, Ronald; Graham, Michael; Hakami, Nasrollah; Kletzel, Morris; Mahoney, Donald; Newman, Edward; Ravindranath, Yaddanapudi; Camitta, Bruce

    2008-01-01

    At concentrations >0.1 mM, Hydroxyurea (HU) enhances the accumulation of cytosine arabinoside (ara-C) in leukemia cells in vitro. This study of children with refractory acute leukemia was designed to take advantage of this biochemical modulation. A fixed dose of HU and an escalating dose of ara-C were used. Oral HU, 1200 mg/m2 was followed 2 hours later by ara-C, 250-3100 mg/m2 intravenously in 15 minutes. The combination was given on days 1,2,3 and 8,9,10. Thirty-three children (26 ALL, 7 AN...

  3. Chemotherapy for Initial Induction Failures in Childhood Acute Lymphoblastic Leukemia: a Children’s Oncology Group Study (POG 8764)

    OpenAIRE

    Joyce, Michael; Pollock, Brad H.; Devidas, Meenakshi; Buchanan, George; Camitta, Bruce

    2013-01-01

    Children with acute lymphocytic leukemia (ALL) who fail to enter remission have a poor prognosis. In a previous study, 9 of 14 children with induction failure entered remission after teniposide (VM26) plus cytosine arabinoside (Ara-C). We attempted to confirm these results. Twenty children received teniposide (200 mg/m2/day IV) for 3 days and cytosine arabinoside (100 mg/m2/day continuous IV infusion) for 7 days. There were 3 complete and 3 partial responses. Two additional patients achieved ...

  4. Cortico-amygdala coupling as a marker of early relapse risk in cocaine-addicted individuals

    Directory of Open Access Journals (Sweden)

    Meredith J Mchugh

    2014-02-01

    Full Text Available Addiction to cocaine is a chronic condition characterized by high rates of early relapse. This study builds on efforts to identify neural markers of relapse risk by studying resting state functional connectivity (rsFC in neural circuits arising from the amygdala; a brain region implicated in relapse-related processes including craving and reactivity to stress following acute and protracted withdrawal from cocaine. Whole-brain resting-state fMRI connectivity (6 min was assessed in 45 cocaine-addicted individuals and 22 healthy controls. Cocaine-addicted individuals completed scans in the final week of a residential treatment episode. To approximate preclinical models of relapse-related circuitry separate seeds were derived for the left and right basolateral (BLA and corticomedial (CMA amygdala. Participants also completed the Iowa Gambling Task, Wisconsin Card Sorting Test, Cocaine Craving Questionnaire, Obsessive Compulsive Cocaine Use scale, Temperament and Character Inventory and the NEO-PI-R. Relapse within the first 30 days post-treatment (n = 24 was associated with reduced rsFC between the left CMA and ventromedial prefrontal cortex/rostral anterior cingulate cortex (vmPFC/rACC relative to cocaine-addicted individuals who remained abstinent (non-relapse, n = 21. Non-relapse participants evidenced reduced rsFC between the bilateral BLA and visual processing regions (lingual gyrus/cuneus compared to controls and relapsed participants. Early relapse was associated with fewer years of education but unrelated to trait reactivity to stress, neurocognitive and clinical characteristics or cocaine use history. Findings suggest that rsFC within neural circuits implicated in preclinical models of relapse may provide a promising marker of relapse risk in cocaine-addicted individuals. Future efforts to replicate the current findings and alter connectivity within these circuits may yield novel interventions and improve treatment outcomes.

  5. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on behavior

    International Nuclear Information System (INIS)

    Mullenix, P.J.; Kernan, W.J.; Tassinari, M.S.; Schunior, A.; Waber, D.P.; Howes, A.; Tarbell, N.J.

    1990-01-01

    Central nervous system prophylactic therapy used in the treatment of acute lymphoblastic leukemia can reduce intelligence quotient scores and impair memory and attention in children. Cranial irradiation, intrathecal methotrexate, and steroids are commonly utilized in acute lymphoblastic leukemia therapy. How they induce neurotoxicity is unknown. This study employs an animal model to explore the induction of neurotoxicity. Male and female Sprague-Dawley rats at 17 and 18 days of age were administered 18 mg/kg prednisolone, 2 mg/kg methotrexate, and 1000 cGy cranial irradiation. Another 18-day-old group was administered 1000 cGy cranial irradiation but no drugs. Matching controls received saline and/or a sham exposure to radiation. All animals at 6 weeks and 4 months of age were tested for alterations in spontaneous behavior. A computer pattern recognition system automatically recorded and classified individual behavioral acts displayed during exploration of a novel environment. Measures of behavioral initiations, total time, and time structure were used to compare treated and control animals. A permanent sex-specific change in the time structure of behavior was induced by the prednisolone, methotrexate, and radiation treatment but not by radiation alone. Unlike hyperactivity, the effect consisted of abnormal clustering and dispersion of acts in a pattern indicative of disrupted development of sexually dimorphic behavior. This study demonstrates the feasibility of an animal model delineating the agent/agents responsible for the neurotoxicity of central nervous system prophylactic therapy

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

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    Jessica Purizaca

    2013-01-01

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

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

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    Vargha-Khadem Faraneh

    2011-10-01

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

  8. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on growth and craniofacial proportion

    International Nuclear Information System (INIS)

    Schunior, A.; Zengel, A.E.; Mullenix, P.J.; Tarbell, N.J.; Howes, A.; Tassinari, M.S.

    1990-01-01

    Many long term survivors of childhood acute lymphoblastic leukemia have short stature, as well as craniofacial and dental abnormalities, as side effects of central nervous system prophylactic therapy. An animal model is presented to assess these adverse effects on growth. Cranial irradiation (1000 cGy) with and without prednisolone (18 mg/kg i.p.) and methotrexate (2 mg/kg i.p.) was administered to 17- and 18-day-old Sprague-Dawley male and female rats. Animals were weighed 3 times/week. Final body weight and body length were measured at 150 days of age. Femur length and craniofacial dimensions were measured directly from the bones, using calipers. For all exposed groups there was a permanent suppression of weight gain with no catch-up growth or normal adolescent growth spurt. Body length was reduced for all treated groups, as were the ratios of body weight to body length and cranial length to body length. Animals subjected to cranial irradiation exhibited microcephaly, whereas those who received a combination of radiation and chemotherapy demonstrated altered craniofacial proportions in addition to microcephaly. Changes in growth patterns and skeletal proportions exhibited sexually dimorphic characteristics. The results indicate that cranial irradiation is a major factor in the growth failure in exposed rats, but chemotherapeutic agents contribute significantly to the outcome of growth and craniofacial dimensions

  9. Shorter maintenance therapy in childhood Acute Lymphoblastic Leukemia. The experience of the prospective, randomized Brazilian GBTLI ALL-93 protocol.

    Directory of Open Access Journals (Sweden)

    Silvia Regina Brandalise

    2016-10-01

    Full Text Available Maintenance therapy is an important phase of the childhood ALL treatment, requiring 2-year long therapy adherence of the patients and families. Weekly methotrexate (MTX with daily 6-mercaptopurine (6MP constitutes the backbone of maintenance therapy. Reduction in the maintenance therapy could overweight problems related with poverty of children with ALL living in Limited-Income countries (LIC. Objective: To compare, prospectively, the EFS rates of children with ALL treated according to two maintenance regimens: 18 vs 24 months duration. Materials and Methods: From October 1993 to September 1999, 867 consecutive untreated ALL patients 10 years and high WBC at diagnosis. Overall death in remission rate was 6.85% (56 patients. Deaths during maintenance were 13 in group 1 and 12 in group 2, all due to infection. Over 15 years of follow-up, two patients both from Group 2 presented a second malignancy (Hodgkin’s disease and thyroid carcinoma after 8.3 and 11 years off therapy, respectively. Conclusion: Six-month reduction of maintenance therapy in ALL children treated according to the GBTLI ALL-93 protocol, provided the same overall outcome as 2-year duration regimen.

  10. Functional symptoms in clinically definite MS--pseudo-relapse syndrome.

    LENUS (Irish Health Repository)

    Merwick, A

    2012-02-03

    Although the diagnostic criteria for multiple sclerosis (MS) have become more formalized and sensitive in the era of magnetic resonance imaging (MRI) scanning, the assessment of individual relapses may not always be straightforward or easily linked to a particular lesion seen on imaging. In addition, acute episodes often have to be assessed outside of normal working hours or when the individual patients usual medical team is not available. Often the emergency department physicians have little formal neurological training and are under time pressure to get patients through the system as quickly as possible. It is therefore possible to mislabel functional symptoms as being true relapses. To illustrate scenarios of possible pseudo-relapse, three clinical vignettes are described. Misclassification of functional symptoms as relapse carries a number of inherent risks. Functional symptoms can be multifactorial and may cause a burden of disease. A multidisciplinary approach may be useful in minimizing unnecessary harm and identify if there is more than meets the eye to an episode of clinical deterioration.

  11. Molecular Therapeutic Approaches for Pediatric Acute Myeloid Leukemia

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    Sarah K Tasian

    2014-03-01

    Full Text Available Approximately two thirds of children with acute myeloid leukemia (AML are cured with intensive multi-agent chemotherapy. However, primary chemorefractory and relapsed AML remains a significant source of childhood cancer mortality, highlighting the need for new therapies. Further therapy intensification with traditional cytotoxic agents is not feasible given the potential for significant toxicity to normal tissues with conventional chemotherapy and the risk for long-term end-organ dysfunction. Significant emphasis has been placed upon the development of molecularly targeted therapeutic approaches for adults and children with high-risk subtypes of AML with the goal of improving remission induction and minimizing relapse. Several promising agents are currently in clinical testing or late preclinical development for AML, including monoclonal antibodies against leukemia cell surface proteins, kinase inhibitors, proteasome inhibitors, epigenetic agents, and chimeric antigen receptor engineered T cell immunotherapies. Many of these therapies have been specifically tested in children with relapsed/refractory AML via phase 1 and 2 trials with a smaller number of new agents under phase 3 evaluation for children with de novo AML. Although successful identification and implementation of new drugs for children with AML remains a formidable challenge, enthusiasm for novel molecular therapeutic approaches is great given the potential for significant clinical benefit for children who will otherwise fail standard therapy.

  12. Water, sanitation and hygiene interventions for acute childhood diarrhea: a systematic review to provide estimates for the Lives Saved Tool.

    Science.gov (United States)

    Darvesh, Nazia; Das, Jai K; Vaivada, Tyler; Gaffey, Michelle F; Rasanathan, Kumanan; Bhutta, Zulfiqar A

    2017-11-07

    In the Sustainable Development Goals (SDGs) era, there is growing recognition of the responsibilities of non-health sectors in improving the health of children. Interventions to improve access to clean water, sanitation facilities, and hygiene behaviours (WASH) represent key opportunities to improve child health and well-being by preventing the spread of infectious diseases and improving nutritional status. We conducted a systematic review of studies evaluating the effects of WASH interventions on childhood diarrhea in children 0-5 years old. Searches were run up to September 2016. We screened the titles and abstracts of retrieved articles, followed by screening of the full-text reports of relevant studies. We abstracted study characteristics and quantitative data, and assessed study quality. Meta-analyses were performed for similar intervention and outcome pairs. Pooled analyses showed diarrhea risk reductions from the following interventions: point-of-use water filtration (pooled risk ratio (RR): 0.47, 95% confidence interval (CI): 0.36-0.62), point-of-use water disinfection (pooled RR: 0.69, 95% CI: 0.60-0.79), and hygiene education with soap provision (pooled RR: 0.73, 95% CI: 0.57-0.94). Quality ratings were low or very low for most studies, and heterogeneity was high in pooled analyses. Improvements to the water supply and water disinfection at source did not show significant effects on diarrhea risk, nor did the one eligible study examining the effect of latrine construction. Various WASH interventions show diarrhea risk reductions between 27% and 53% in children 0-5 years old, depending on intervention type, providing ample evidence to support the scale-up of WASH in low and middle-income countries (LMICs). Due to the overall low quality of the evidence and high heterogeneity, further research is required to accurately estimate the magnitude of the effects of these interventions in different contexts.

  13. Parallel targeted next generation sequencing of childhood and adult acute myeloid leukemia patients reveals uniform genomic profile of the disease.

    Science.gov (United States)

    Marjanovic, Irena; Kostic, Jelena; Stanic, Bojana; Pejanovic, Nadja; Lucic, Bojana; Karan-Djurasevic, Teodora; Janic, Dragana; Dokmanovic, Lidija; Jankovic, Srdja; Vukovic, Nada Suvajdzic; Tomin, Dragica; Perisic, Ognjen; Rakocevic, Goran; Popovic, Milos; Pavlovic, Sonja; Tosic, Natasa

    2016-10-01

    The age-specific differences in the genetic mechanisms of myeloid leukemogenesis have been observed and studied previously. However, NGS technology has provided a possibility to obtain a large amount of mutation data. We analyzed DNA samples from 20 childhood (cAML) and 20 adult AML (aAML) patients, using NGS targeted sequencing. The average coverage of high-quality sequences was 2981 × per amplicon. A total of 412 (207 cAML, 205 aAML) variants in the coding regions were detected; out of which, only 122 (62 cAML and 60 aAML) were potentially protein-changing. Our results confirmed that AML contains small number of genetic alterations (median 3 mutations/patient in both groups). The prevalence of the most frequent single gene AML associated mutations differed in cAML and aAML patient cohorts: IDH1 (0 % cAML, 5 % aAML), IDH2 (0 % cAML, 10 % aAML), NPM1 (10 % cAML, 35 % aAML). Additionally, potentially protein-changing variants were found in tyrosine kinase genes or genes encoding tyrosine kinase associated proteins (JAK3, ABL1, GNAQ, and EGFR) in cAML, while among aAML, the prevalence is directed towards variants in the methylation and histone modifying genes (IDH1, IDH2, and SMARCB1). Besides uniform genomic profile of AML, specific genetic characteristic was exclusively detected in cAML and aAML.

  14. The Cost of Relapse in Schizophrenia.

    Science.gov (United States)

    Pennington, Mark; McCrone, Paul

    2017-09-01

    Schizophrenia is a chronic and debilitating mental illness characterised by periods of relapse that require resource intensive management. Quantifying the cost of relapse is central to the evaluation of the cost effectiveness of treating schizophrenia. We aimed to undertake a comprehensive search of the available literature on the cost of relapse. We performed a search on multiple databases (MEDLINE, Embase, PsycINFO and Health Management Information Consortium) for any study reporting a cost of relapse or data from which such a cost could be calculated. Costs are reported in 2015 international dollars. We found 16 studies reporting costs associated with relapse over a defined period of time and identified a cost associated with hospitalisation for relapse in 43 studies. Eight clinical decision analyses also provided cost estimates. Studies from the US report excess costs of relapse of $6033-$32,753 (2015 Purchasing Power Parity dollars [PPP$]) over periods of 12-15 months. European studies report excess costs of $8665-$18,676 (2015 PPP$) over periods of 6-12 months. Estimates of the cost of hospitalisation for relapse are more diverse, and associated with marked differences in typical length of stay across jurisdictions. Wide ranges in the estimated cost of relapse may reflect differences in sample section and relapse definition as well as practice styles and differences in resource costs. Selection of the most appropriate cost estimate should be guided by the definition of relapse and the analysis setting.

  15. Treatment strategies and regimens of graduated intensity for childhood acute lymphoblastic leukemia in low-income countries: A proposal.

    Science.gov (United States)

    Hunger, Stephen P; Sung, Lillian; Howard, Scott C

    2009-05-01

    Cure rates for children with acute lymphoblastic leukemia (ALL) are 80-85% in high-income countries (HICs) in North America and Western Europe. However, cure rates are much lower in many low-income countries (LICs), where most cases of ALL occur. Over the past several decades partnerships ("twinning") between HIC and LIC pediatric oncology programs have led to major improvements in outcome for children with ALL in some LICs, often by developing time and resource intensive relationships that allow LIC centers to treat children with regimens similar or identical to those used in HICs. However, the resources are not available in most LICs to allow immediate introduction of intensive ALL treatment regimens similar to those used in HICs. With these thoughts in mind, we present a proposal for a systematic and graduated approach to ALL diagnosis, risk classification, and treatment in LICs. We have based the strategy and the proposed regimens on those developed by the Children's Cancer Group (CCG) and Children's Oncology Group (COG) over the past several decades, beginning with a first level regimen similar to CCG therapy of the early 1980s and then layering on successive treatment intensifications proven effective in randomized clinical trials. Simple monitoring rules are included to help centers decide when they are ready to add new treatment components. This proposal provides a framework that LIC centers can use to provide effective ALL therapy, particularly in regions of the world where few children are currently being cured. (c) 2009 Wiley-Liss, Inc.

  16. Associating Physical Activity Levels with Motor Performance and Physical Function in Childhood Survivors of Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Hung, Stanley H; Rankin, Anne; Virji-Babul, Naznin; Pritchard, Sheila; Fryer, Christopher; Campbell, Kristin L

    2017-01-01

    Purpose: This cross-sectional, observational study investigated whether physical activity (PA) levels are associated with motor performance and physical function in children after treatment for acute lymphoblastic leukemia (ALL). Method: Participants aged 8-13 years who had completed treatment for ALL (3-36 months post-treatment) were tested at their oncology long-term follow-up appointment at the British Columbia Children's Hospital. PA level was measured using the Physical Activity Questionnaire for Older Children (PAQ-C). Motor performance was measured using the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, Short Form (BOT-2 SF), and physical function was measured using the 6-minute walk test (6MWT). Results: Thirteen children completed testing. PAQ-C scores were not associated with BOT-2 SF or 6MWT performance. Eleven children (85%) performed below the norm for the 6MWT. Children with elevated body mass index had poorer 6MWT but similar PAQ-C scores. Conclusion: PA was not found to be associated with motor performance and physical function. Participants who were overweight or obese had poorer 6MWT performance, which may indicate the need for closer monitoring of post-treatment weight status and physical function in the oncology follow-up setting.

  17. Anxiety, depression, stress, and cortisol levels in mothers of children undergoing maintenance therapy for childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Neu, Madalynn; Matthews, Ellyn; King, Nancy A; Cook, Paul F; Laudenslager, Mark L

    2014-01-01

    The purpose of this study was to compare anxiety, depression, and stress between mothers of children during maintenance treatment for acute lymphoblastic leukemia (ALL) and matched controls. Twenty-six mothers were recruited from the hematology unit at a children's hospital, and 26 mothers were recruited from the community. Participants were matched to their child's age and gender. Mothers completed the Hospital Anxiety and Depression Scale, the Perceived Stress Sale, and collected salivary cortisol 4 times a day for 3 consecutive days. Compared with mothers of healthy children, anxiety scores did not differ (P=.10), but depression scores were higher (P=.003) in mothers of children with ALL. More mothers in the ALL group scored above the cutoff of 7 indicating clinical anxiety (46%) and depressive symptoms (27%). A trend toward increased stress was found in mothers in the ALL group. No difference was found in overall daily cortisol (area under the curve), daily decrease in cortisol (slope), and cortisol awakening response. Mothers of children with ALL experienced emotional symptoms many months after the initial diagnosis.

  18. Assessment of mercaptopurine (6MP) metabolites and 6MP metabolic key-enzymes in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Wojtuszkiewicz, Anna; Barcelos, Ana; Dubbelman, Boas; De Abreu, Ronney; Brouwer, Connie; Bökkerink, Jos P; de Haas, Valerie; de Groot-Kruseman, Hester; Jansen, Gerrit; Kaspers, Gertjan L; Cloos, Jacqueline; Peters, G J

    2014-01-01

    Pediatric acute lymphoblastic leukemia (ALL) is treated with combination chemotherapy including mercaptopurine (6MP) as an important component. Upon its uptake, 6MP undergoes a complex metabolism involving many enzymes and active products. The prognostic value of all the factors engaged in this pathway still remains unclear. This study attempted to determine which components of 6MP metabolism in leukemic blasts and red blood cells are important for 6MP's sensitivity and toxicity. In addition, changes in the enzymatic activities and metabolite levels during the treatment were analyzed. In a cohort (N=236) of pediatric ALL patients enrolled in the Dutch ALL-9 protocol, we studied the enzymes inosine-5'-monophosphate dehydrogenase (IMPDH), thiopurine S-methyltransferase (TPMT), hypoxanthine guanine phosphoribosyl transferase (HGPRT), and purine nucleoside phosphorylase (PNP) as well as thioguanine nucleotides (TGN) and methylthioinosine nucleotides (meTINs). Activities of selected enzymes and levels of 6MP derivatives were measured at various time points during the course of therapy. The data obtained and the toxicity related parameters available for these patients were correlated with each other. We found several interesting relations, including high concentrations of two active forms of 6MP--TGN and meTIN--showing a trend toward association with better in vitro antileukemic effect of 6MP. High concentrations of TGN and elevated activity of HGPRT were found to be significantly associated with grade III/IV leucopenia. However, a lot of data of enzymatic activities and metabolite concentrations as well as clinical toxicity were missing, thereby limiting the number of assessed relations. Therefore, although a complex study of 6MP metabolism in ALL patients is feasible, it warrants more robust and strict data collection in order to be able to draw more reliable conclusions.

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

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    M Belayet Hossain

    2017-01-01

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

  20. Father's occupational exposure to carcinogenic agents and childhood acute leukemia: a new method to assess exposure (a case-control study

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    Rodriguez-Rivera Maria

    2008-01-01

    Full Text Available Abstract Background Medical research has not been able to establish whether a father's occupational exposures are associated with the development of acute leukemia (AL in their offspring. The studies conducted have weaknesses that have generated a misclassification of such exposure. Occupations and exposures to substances associated with childhood cancer are not very frequently encountered in the general population; thus, the reported risks are both inconsistent and inaccurate. In this study, to assess exposure we used a new method, an exposure index, which took into consideration the industrial branch, specific position, use of protective equipment, substances at work, degree of contact with such substances, and time of exposure. This index allowed us to obtain a grade, which permitted the identification of individuals according to their level of exposure to known or potentially carcinogenic agents that are not necessarily specifically identified as risk factors for leukemia. The aim of this study was to determine the association between a father's occupational exposure to carcinogenic agents and the presence of AL in their offspring. Methods From 1999 to 2000, a case-control study was performed with 193 children who reside in Mexico City and had been diagnosed with AL. The initial sample-size calculation was 150 children per group, assessed with an expected odds ratio (OR of three and a minimum exposure frequency of 15.8%. These children were matched by age, sex, and institution with 193 pediatric surgical patients at secondary-care hospitals. A questionnaire was used to determine each child's background and the characteristics of the father's occupation(s. In order to determine the level of exposure to carcinogenic agents, a previously validated exposure index (occupational exposure index, OEI was used. The consistency and validity of the index were assessed by a questionnaire comparison, the sensory recognition of the work area, and an

  1. Health-seeking behaviour and community perceptions of childhood undernutrition and a community management of acute malnutrition (CMAM) programme in rural Bihar, India: a qualitative study.

    Science.gov (United States)

    Burtscher, Doris; Burza, Sakib

    2015-12-01

    Since 2009, Médecins Sans Frontières has implemented a community management of acute malnutrition (CMAM) programme in rural Biraul block, Bihar State, India that has admitted over 10 000 severely malnourished children but has struggled with poor coverage and default rates. With the aim of improving programme outcomes we undertook a qualitative study to understand community perceptions of childhood undernutrition, the CMAM programme and how these affected health-seeking behaviour. Semi-structured and narrative interviews were undertaken with families of severely malnourished children, non-undernourished children and traditional and allopathic health-care workers. Analysis of transcripts was by qualitative content analysis. Biraul, Bihar State, India, 2010. One hundred and fifty people were interviewed in individual or group discussions during fifty-eight interviews. Undernutrition was not viewed as a disease; instead, local disease concepts were identified that described the clinical spectrum of undernutrition. These concepts informed perception, so caregivers were unlikely to consult health workers if children were 'only skinny'. Hindu and Muslim priests and other traditional health practitioners were more regularly consulted and perceived as easier to access than allopathic health facilities. Senior family members and village elders had significant influence on the health-seeking behaviour of parents of severely malnourished children. The results reaffirm how health education and CMAM programmes should encompass local disease concepts, beliefs and motivations to improve awareness that undernutrition is a disease and one that can be treated. CMAM is well accepted by the community; however, programmes must do better to engage communities, including traditional healers, to enable development of a holistic approach within existing social structures.

  2. Multiple-clone activation of hypnozoites is the leading cause of relapse in Plasmodium vivax infection.

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    Flávia Carolina F de Araujo

    Full Text Available BACKGROUND: Plasmodium vivax infection is characterized by a dormant hepatic stage, the hypnozoite that is activated at varying periods of time after clearance of the primary acute blood-stage, resulting in relapse. Differentiation between treatment failure and new infections requires characterization of initial infections, relapses, and clone multiplicity in vivax malaria infections. METHODOLOGY/PRINCIPAL FINDINGS: Parasite DNA obtained from primary/relapse paired blood samples of 30 patients with P. vivax infection in Brazil was analyzed using 10 molecular markers (8 microsatellites and MSP-1 blocks 2 and 10. Cloning of PCR products and genotyping was used to identify low-frequency clones of parasites. We demonstrated a high frequency of multiple-clone infections in both primary and relapse infections. Few alleles were identified per locus, but the combination of these alleles produced many haplotypes. Consequently, the majority of parasites involved in relapse showed haplotypes that were distinct from those of primary infections. Plasmodium vivax relapse was characterized by temporal variations in the predominant parasite clones. CONCLUSIONS/SIGNIFICANCE: The high rate of low frequency alleles observed in both primary and relapse infections, along with temporal variation in the predominant alleles, might be the source of reported heterologous hypnozoite activation. Our findings complicate the concept of heterologous activation, suggesting the involvement of undetermined mechanisms based on host or environmental factors in the simultaneous activation of multiple clones of hypnozoites.

  3. Acute Pancreatitis in Children

    Science.gov (United States)

    ... a feeding tube or an IV to prevent malnutrition and improve healing. Does my child have to ... Acute Pancreatitis in Children Chronic Pancreatitis in Children Childhood Inherited Disorders Pancreatic Cancer Pancreatic Cancer Risks and ...

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

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Heyman, Mats; Kristinsson, Jon

    2009-01-01

    The importance of maintenance therapy for higher risk childhood acute lymphoblastic leukemia (ALL) is uncertain. Between 1992 and 2001 the Nordic Society for Pediatric Haematology/Oncology compared in a nonrandomized study conventional oral methotrexate (MTX)/6-mercaptopurine (6MP) maintenance...... therapy (P=0.04) were both related to an increased risk of an event (overall P value of the Cox model: 0.003), whereas neither sex, age at diagnosis, administration of central nervous system irradiation, nor presence of a day 15 bone marrow with > or =25% versus

  5. Peri-optic nerve infiltration during leukaemic relapse: MRI diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Madani, A.; Christophe, C. [Department of Imaging, Hopital Universitaire des Enfants Reine Fabiola, Brussels (Belgium); Ferster, A.; Dan, B. [Department of Paediatrics, Hopital Universitaire des Enfants Reine Fabiola, Brussels (Belgium)

    2000-01-01

    Background. A 10-year-old boy with a history of acute lymphoblastic leukaemia (ALL), but without previous evidence of central nervous system involvement, presented with seizures 3 years after complete remission. Materials and methods. MRI showed bilateral enlargement of the optic nerves despite normal ophthalmological examination. Results. Only the third cerebrospinal fluid examination showed 2 % blasts without concomitant bone-marrow infiltration. Enlargement of the optic nerves was consistent with bilateral leukaemic peri-optic nerve infiltration. The appearances returned to normal after chemotherapy. Conclusion. The optic nerves are a potential site of relapse in patients with systemic and meningeal ALL, even in the absence of ophthalmological signs. (orig.)

  6. Late adverse effects of whole cranial irradiation in childhood hematological disorders

    Energy Technology Data Exchange (ETDEWEB)

    Someya, Masanori; Nakata, Kensei; Nagakura, Hisayasu; Oouchi, Atsushi; Sakata, Kohichi; Hareyama, Masato [Sapporo Medical Coll. (Japan)

    2003-03-01

    The purpose of this study was to examine the late adverse effects of childhood hematological disorders treated with chemotherapy and radiotherapy including whole cranial irradiation at Sapporo Medical University Hospital. Twenty-eight patients were treated with chemotherapy and 18-24 Gy of prophylactic cranial irradiation (PCI) for acute lymphoblastic leukemia (ALL), and 14 patients were treated with 3-12.8 Gy of total body irradiation (TBI) and bone marrow transplantation (BMT) for ALL, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), myelodysplastic syndrome (MDS), malignant lymphoma, and aplastic anemia (AA). Age at diagnosis ranged from 2 to 15 years old, and 28 were males and 14 were females. All patients were disease-free more than 2 years after diagnosis. Of 42 patients, 4 patients had decreased height (less than -2 S.D.), 3 patients required hormone replacement therapy, 2 patients had mental retardation, 3 patients had leukoencephalopathy, and 1 patient had a second malignancy. Except for the cases of decreased height, 3 of 7 late adverse effects were occurred in patients who had relapse of disease, and the risk of the adverse effects seemed to be higher for those patients whose doses of PCI were 22 Gy or more, or who received an additional craniospinal irradiation due to relapse of disease, and 18 Gy of PCI did not increase the risk of adverse effects. (author)

  7. Effectiveness of ready-to-use therapeutic food compared to a corn/soy-blend-based pre-mix for the treatment of childhood moderate acute malnutrition in Niger.

    Science.gov (United States)

    Nackers, Fabienne; Broillet, France; Oumarou, Diakité; Djibo, Ali; Gaboulaud, Valérie; Guerin, Philippe J; Rusch, Barbara; Grais, Rebecca F; Captier, Valérie

    2010-12-01

    Standard nutritional treatment of moderate acute malnutrition (MAM) relies on fortified blended flours though their importance to treat this condition is a matter of discussion. With the newly introduced World Health Organization growth standards, more children at an early stage of malnutrition will be treated following the dietary protocols as for severe acute malnutrition, including ready-to-use therapeutic food (RUTF). We compared the effectiveness of RUTF and a corn/soy-blend (CSB)-based pre-mix for the treatment of MAM in the supplementary feeding programmes (SFPs) supported by Médecins Sans Frontières, located in the Zinder region (south of Niger). Children measuring 65 to childhood MAM in Niger, RUTF resulted in a higher weight gain, a higher recovery rate, a shorter length of stay and a lower transfer rate to the I-TFC compared to a CSB pre-mix. This might have important implications on the efficacy and the quality of SFPs.

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

    DEFF Research Database (Denmark)

    Obro, Nina F; Ryder, Lars P; Madsen, Hans O

    2012-01-01

    Reduction in minimal residual disease, measured by real-time quantitative PCR or flow cytometry, predicts prognosis in childhood B-cell precursor acute lymphoblastic leukemia. We explored whether cells reported as minimal residual disease by flow cytometry represent the malignant clone harboring...... clone-specific genomic markers (53 follow-up bone marrow samples from 28 children with B-cell precursor acute lymphoblastic leukemia). Cell populations (presumed leukemic and non-leukemic) were flow-sorted during standard flow cytometry-based minimal residual disease monitoring and explored by PCR and....../or fluorescence in situ hybridization. We found good concordance between flow cytometry and genomic analyses in the individual flow-sorted leukemic (93% true positive) and normal (93% true negative) cell populations. Four cases with discrepant results had plausible explanations (e.g. partly informative...

  9. Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children.

    NARCIS (Netherlands)

    Kyrieleis, H.A.; Lowik, M.M.; Pronk, I.; Cruysberg, J.R.M.; Kremer, J.A.M.; Oyen, W.J.G.; Heuvel, L.P.W.J. van den; Wetzels, J.F.M.; Levtchenko, E.N.

    2009-01-01

    BACKGROUND AND OBJECTIVES: Frequently relapsing and steroid-dependent minimal-change nephrotic syndrome (MCNS) that originates in childhood can persist after puberty in >20% of patients. These patients require immunosuppressive treatment during several decades of their life. We examined long-term

  10. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... CIS) Newly Diagnosed Diagnosing Tools Other Conditions to Rule Out For Clinicians Treating MS Comprehensive Care Find ... CSF) Evoked Potentials (EP) d Other Conditions to Rule Out Lyme Disease Lupus Neuromyelitis Optica Acute Disseminated ...

  11. Methotrexate-induced acute toxic leukoencephalopathy

    Directory of Open Access Journals (Sweden)

    Parag R Salkade

    2012-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is one of the most common malignancies of childhood, which is treated with high doses of methotrexate (MTX, as it crosses the blood-brain barrier and can be administered intravenously and via intrathecal route to eradicate leukemic cells from central nervous system (CNS. Additionally, high doses of MTX not only prevent CNS recurrence but also hematologic relapses. Although, standard treatment protocol for ALL includes multimodality therapy, MTX is usually associated with neurotoxicity and affects periventricular deep white matter region. Methotrexate-induced ′acute toxic leukoencephalopathy′ has varying clinical manifestations ranging from acute neurological deficit to seizures or encephalopathy. Diffusion weighted magnetic resonance imaging (DW-MRI is widely available and routinely used in clinical practice to identify acute stroke and also to distinguish acute stroke from non-stroke like conditions. We report a local teenage Chinese girl who developed 2 discrete episodes of left upper and lower limb weakness with left facial nerve paresis after receiving the 2 nd and 3 rd cycle of high dose of intravenous and intrathecal methotrexate, without having cranial irradiation. After each episode of her neurological deficit, the DW-MRI scan showed focal restricted diffusion in right centrum semiovale. Her left sided focal neurological deficit and facial nerve paresis almost completely subsided on both these occasions within 3 days of symptom onset. Follow-up DW-MRI, after her neurological recovery, revealed almost complete resolution of previously noted restricted diffusion in right centrum semiovale, while the lesion was not evident on concurrent T2W (T2-weighted and FLAIR (Fluid-Attenuated Inversion recovery sequences, nor showed any post contrast enhancement on post gadolinium enhanced T1W (T1-weighted sequences. No residual neurological deficit or intellectual impairment was identified on clinical follow up

  12. Prognostic significance of P2RY8-CRLF2 and CRLF2 overexpression may vary across risk subgroups of childhood B-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Dou, Hu; Chen, Xi; Huang, Yi; Su, Yongchun; Lu, Ling; Yu, Jie; Yin, Yibing; Bao, Liming

    2017-02-01

    The cytokine receptor-like factor 2 (CRLF2) gene plays an important role in early B-cell development. Aberrations in CRLF2 activate the JAK-STAT signaling pathway that contributes to B-cell acute lymphoblastic leukemia (B-ALL). The prognostic significance of CRLF2 overexpression and P2RY8-CRLF2 fusion in various B-ALL risk subgroups has not been well established. Two hundred seventy-one patients with newly diagnosed childhood B-ALL were enrolled from a Chinese population. The prevalence of CRLF2 overexpression, CRLF2-P2RY8 fusion, CRLF2 F232C mutation, and JAK2 and IL7R mutational status were analyzed, and the prognostic impact of CRLF2 overexpression and P2RY8-CRLF2 on B-ALL was evaluated by assessing their influence on overall survival and event-free survival. CRLF2 overexpression and P2RY8-CRLF2 were found in 19% and 10%, respectively, in the whole cohort. No correlation between CRLF2 overexpression and P2RY8-CRLF2 was observed. CRLF2 F322C and IL7R mutations were not detected in B-ALL cases overexpressing CRLF2, and no JAK2 mutations were found in the whole cohort either. The results showed that CRLF2 overexpression and P2RY8-CRLF2 were associated with a poor outcome in unselected B-ALL. Moreover, in an intermediate risk B-ALL subgroup P2RY8-CRLF2 was correlated with worse survival, whereas in high- and low-risk subgroups, CRLF2 overexpression predicted a poor outcome. Our findings suggest that P2RY8-CRLF2 is an independent prognostic indicator in intermediate risk B-ALL, while CRLF2 overexpression is correlated with an inferior outcome in high- or low-risk B-ALL. Our study demonstrates that the impact of P2RY8-CRLF2 and CRLF2 overexpression on B-ALL survival may differ across risk subgroups. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Evaluation of Endocrine Late Complications in Childhood Acute Lymphoblastic Leukemia Survivors: A Report of a Single-Center Experience and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Cengiz Bayram

    2017-03-01

    Full Text Available Objective: Improvement in long-term survival in patients with acute lymphoblastic leukemia (ALL in childhood has led to the need for monitorization of treatment-related morbidity and mortality. In the current study, we aimed to evaluate endocrine side effects of treatment in ALL survivors who were in remission for at least 2 years. Materials and Methods: Sixty patients diagnosed with ALL, who were in remission for at least 2 years, were cross-sectionally evaluated for long-term endocrine complications. Results: The median age of the patients at the time of diagnosis, at the time of chemotherapy completion, and at the time of the study was 5 years (minimum-maximum: 1.7-13, 8 years (minimummaximum: 4.25-16, and 11.7 years (minimum-maximum: 7-22, respectively, and median follow-up time was 4 years (minimummaximum: 2-10.1. At least one complication was observed in 81.6% of patients. Vitamin D insufficiency/deficiency (46.6%, overweight/ obesity (33.3%, and dyslipidemia (23.3% were the three most frequent endocrine complications. Other complications seen in our patients were hyperparathyroidism secondary to vitamin D deficiency (15%, insulin resistance (11.7%, hypertension (8.3%, short stature (6.7%, thyroid function abnormality (5%, precocious puberty (3.3%, and decreased bone mineral density (1.7%. There were no statistically significant correlations between endocrine complications and age, sex, and radiotherapy, except vitamin D insufficiency/deficiency, which was significantly more frequent in pubertal ALL survivors compared to prepubertal ALL survivors (57.5% and 25%, respectively, p=0.011. Conclusion: A high frequency of endocrine complications was observed in the current study. The high frequency of late effects necessitates long-term surveillance of this population to better understand the incidence of late-occurring events and the defining of high-risk features that can facilitate developing intervention strategies for early detection and

  14. Outcome after failure of allogeneic hematopoietic stem cell transplantation in children with acute leukemia: a study by the société Francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

    Science.gov (United States)

    Roux, C; Tifratene, K; Socié, G; Galambrun, C; Bertrand, Y; Rialland, F; Jubert, C; Pochon, C; Paillard, C; Sirvent, A; Nelken, B; Vannier, J P; Freycon, C; Beguin, Y; Raus, N; Yakoub-Agha, I; Mohty, M; Dalle, J-H; Michel, G; Pradier, C; Peffault de Latour, R; Rohrlich, P-S

    2017-05-01

    Allogeneic hematopoietic stem cell transplantation (SCT) contributes to improved outcome in childhood acute leukemia (AL). However, therapeutic options are poorly defined in the case of post-transplantation relapse. We aimed to compare treatment strategies in 334 consecutive children with acute leukemia relapse or progression after SCT in a recent 10-year period. Data could be analyzed in 288 patients (157 ALL, 123 AML and 8 biphenotypic AL) with a median age of 8.16 years at transplantation. The median delay from first SCT to relapse or progression was 182 days. The treatment consisted of chemotherapy alone (n=108), chemotherapy followed by second SCT (n=70), supportive/palliative care (n=67), combination of chemotherapy and donor lymphocyte infusion (DLI; n=30), or isolated reinfusion of donor lymphocytes (DLI; n=13). The median OS duration after relapse was 164 days and differed according to therapy: DLI after chemotherapy=385 days, second allograft=391 days, chemotherapy=174 days, DLI alone=140 days, palliative care=43 days. A second SCT or a combination of chemotherapy and DLI yielded similar outcome (hazard ratio (HR)=0.85, P=0.53) unlike chemotherapy alone (HR=1.43 P=0.04), palliative care (HR=4.24, P<0.0001) or isolated DLI (HR=1,94, P<0.04). Despite limitations in this retrospective setting, strategies including immunointervention appear superior to other approaches, mostly in AML.

  15. Safety and Pharmacokinetics of the Antisense Oligonucleotide (ASO) LY2181308 as a Single-Agent or in Combination with Idarubicin and Cytarabine in Patients with Refractory or Relapsed Acute Myeloid Leukemia (AML)

    Science.gov (United States)

    Erba, Harry P.; Sayar, Hamid; Juckett, Mark; Lahn, Michael; Andre, Valerie; Callies, Sophie; Schmidt, Shelly; Kadam, Sunil; Brandt, John T.; Van Bockstaele, Dirk; Andreeff, Michael

    2014-01-01

    Summary Survivin is expressed in tumor cells, including acute myeloid leukemia (AML), regulates mitosis, and prevents tumor cell death. The antisense oligonucleotide sodium LY2181308 (LY2181308) inhibits survivin expression and may cause cell cycle arrest and restore apoptosis in AML. Methods In this study, the safety, pharmacokinetics, and pharmacodynamics/efficacy of LY2181308 was examined in AML patients, first in a cohort with monotherapy (n=8) and then post-amendment in a cohort with the combination of cytarabine and idarubicin treatment (n=16). LY2181308 was administered with a loading dosage of 3 consecutive daily infusions of 750 mg followed by weekly intravenous (IV) maintenance doses of 750 mg. Cytarabine 1.5 g/m2 was administered as a 4-hour IV infusion on Days 3, 4, and 5 of Cycle 1, and idarubicin 12 mg/m2 was administered as a 30-minute IV infusion on Days 3, 4, and 5 of Cycle 1. Cytarabine and idarubicin were administered on Days 1, 2, and 3 of each subsequent 28-day cycle. Reduction of survivin was evaluated in peripheral blasts and bone marrow. Results Single-agent LY2181308 was well tolerated and survivin was reduced only in patients with a high survivin expression. In combination with chemotherapy, 4/16 patients had complete responses, 1/16 patients had incomplete responses, and 4/16 patients had cytoreduction. Nine patients died on study: 6 (monotherapy), 3 (combination). Conclusions LY2181308 alone is well tolerated in patients with AML. In combination with cytarabine and idarubicin, LY2181308 does not appear to cause additional toxicity, and has shown some clinical benefit needing confirmation in future clinical trials. PMID:23397500

  16. Clinical and cytogenetic features of pediatric dic(9;20)(p13.2;q11.2)-positive B-cell precursor acute lymphoblastic leukemias: a Nordic series of 24 cases and review of the literature

    DEFF Research Database (Denmark)

    Forestier, Erik; Gauffin, Fredrika; Andersen, Mette K

    2008-01-01

    Although dic(9;20)(p13.2;q11.2) is a characteristic abnormality in childhood B-cell precursor acute lymphoblastic leukemias (BCP ALL), little is known about its clinical impact or the type and frequency of additional aberrations it may occur together with. We here review the clinical and cytogene......Although dic(9;20)(p13.2;q11.2) is a characteristic abnormality in childhood B-cell precursor acute lymphoblastic leukemias (BCP ALL), little is known about its clinical impact or the type and frequency of additional aberrations it may occur together with. We here review the clinical...... a mediastinal mass at diagnosis. Risk group stratification was nonstandard risk in 79%. The event-free survival and overall survival at 5 years for the 24 Nordic cases was 0.62 and 0.82, respectively. Thus, although relapses are quite common, postrelapse treatment of many patients is successful....

  17. Early life adversity influences stress response association with smoking relapse.

    Science.gov (United States)

    al'Absi, Mustafa; Lemieux, Andrine; Westra, Ruth; Allen, Sharon

    2017-11-01

    We examined the hypothesis that stress-related blunting of cortisol in smokers is particularly pronounced in those with a history of severe life adversity. The two aims of this study were first to examine hormonal, craving, and withdrawal symptoms during ad libitum smoking and after the first 24 h of abstinence in smokers who experienced high or low levels of adversity. Second, we sought to examine the relationship between adversity and hypothalamic-pituitary-adrenal (HPA) hormones to predict relapse during the first month of a smoking cessation attempt. Hormonal and self-report measures were collected from 103 smokers (49 women) during ad libitum smoking and after the first 24 h of abstinence. HPA hormones were measured during baseline rest and in response to acute stress in both conditions. All smokers were interested in smoking cessation, and we prospectively used stress response measures to predict relapse during the first 4 weeks of the smoking cessation attempt. The results showed that high adversity was associated with higher distress and smoking withdrawal symptoms. High level of early life adversity was associated with elevated HPA activity, which was found in both salivary and plasma cortisol. Enhanced adrenocorticotropic hormone (ACTH) stress response was evident in high-adversity but not in low-adversity relapsers. This study demonstrated that early life adversity is associated with stress-related HPA responses. The study also demonstrated that, among smokers who experienced a high level of life adversity, heightened ACTH and cortisol responses were linked with increased risk for smoking relapse.

  18. Tumor relapse present in oncologic nasal repair

    International Nuclear Information System (INIS)

    Galvez Chavez, Julio Cesar; Sanchez Wals, Lenia; Monzon Fernandez, Abel Nicolas; Morales Tirado, Roxana

    2009-01-01

    Tumor relapse is one of the more fearsome complications of the oncologic course and also to obscure the life prognosis, causing the loss of many reconstructions and of exhausting the repairing surgical possibilities. The aim of this study was to determine the relapse frequency, the repercussion on the repair and the subsequent medical course of patients operated on malign nasal tumors

  19. Breaking the Rhythm of Depression: Cognitive Behavior Therapy and Relapse Prevention for Depression

    Directory of Open Access Journals (Sweden)

    Claudi L.H. Bockting

    2010-12-01

    Full Text Available A crucial part of the treatment of depression is the prevention of relapse and recurrence. Psychological interventions, especially cognitive behavior therapy (CBT are helpful in preventing relapse and recurrence in depression. The effectivity of four types of relapse prevention cognitive behavior therapy strategies will be addressed, i.e. acute prophylactic cognitive behavior therapy, continuation cognitive behavior therapy, sequential cognitive behavior therapy and cognitive behavior therapy in partial remission.Specific ingredients of three sequential cognitive behavior therapy programs (well-being cognitive therapy, preventive cognitive therapy, and mindfulness-based cognitive therapy will be discussed as applied after remission in patients that experienced previous depressive episodes. Sequential preventive cognitive behavior therapy after acute treatment may be an attractive alternative treatment for many patients who currently use antidepressants for years and years to prevent relapse and recurrence. This is an extremely challenging issue to research thoroughly. Future studies must rule out what intervention for whom is the best protection against relapse and recurrence in depression.

  20. Severe childhood malnutrition

    DEFF Research Database (Denmark)

    Bhutta, Zulfiqar A; Berkley, James A; Bandsma, Robert H J

    2017-01-01

    The main forms of childhood malnutrition occur predominantly in children malnutrition. Here, we use...... the term 'severe malnutrition' to describe these conditions to better reflect the contributions of chronic poverty, poor living conditions with pervasive deficits in sanitation and hygiene, a high prevalence of infectious diseases and environmental insults, food insecurity, poor maternal and fetal...... nutritional status and suboptimal nutritional intake in infancy and early childhood. Children with severe malnutrition have an increased risk of serious illness and death, primarily from acute infectious diseases. International growth standards are used for the diagnosis of severe malnutrition and provide...