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The use of biomarkers in detecting subclinical cardiotoxicity in doxorubicin-based treatment for paediatric patients with acute lymphoblastic leukaemia


The international standard protocol for acute lymphoblastic leukaemia (ALL), the most common haemato-oncological pathology at paediatric age, uses anthracyclines as antitumor agents, potentially associated with early or late onset cardiac damage. Currently, echocardiography is the gold standard in the diagnosis of cardiotoxicity, but several biomarkers are evaluated as a possible replacement, pending more extensive clinical studies. We started a prospective study in order to determine the role of two biomarkers, troponin and heart-type fatty acid binding protein, in the evaluation of cardiotoxicity in children over one year of age, diagnosed with ALL. Between February 2015 and April 2016, 20 patients were enrolled and monitored at diagnosis, during chemotherapy and four months after the end of reinduction, through cardiac evaluation and dosing of those two markers in five different points of the treatment protocol. During the first year of follow-up, the patients did not develop clinical signs of cardiac damage, but the study showed a slight increase in troponin levels during chemotherapy, with the return to baseline value after treatment cessation, and also a correlation with the total dose of anthracyclines given to the patient. On the other hand, the second biomarker, heart-type fatty acid binding protein, did not seem to be useful in detecting subclinical cardiac damage in these patients.

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The impact of immunological and biomolecular investigations on the outcome of children with acute lymphoblastic leukemia - experience of IIIrd Paediatric Clinic Timisoara

References 1. Inaba H, Greaves M, Mullighan CG. Acute lymphoblastic leukaemia. The Lancet. 2013 Jun;381(9881):1943-55. DOI: 10.1016/S0140-6736(12)62187-4 2. Bartram CR, Schrauder A, Köhler R, Schrappe M. Acute lymphoblastic leukemia in children: treatment planning via minimal residual disease assessment. Dtsch Arzteblatt Int. 2012 Oct;109(40):652-8. 3. Harrison CJ. Cytogenetics of paediatric and adolescent acute lymphoblastic leukaemia. Br J Haematol. 2009 Jan;144(2):147-56. DOI: 10.1111/j.1365-2141.2008.07417.x

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Mathematical model to predict methotrexate elimination in children with acute lymphoblastic leukemia

. Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia. Leukemia. 2010;24(2):345-54. DOI: 10.1038/leu.2009.251 12. Mitchell C, Richards S, Harrison CJ, Eden T. Long-term follow-up of the United Kingdom medical research council protocols for childhood acute lymphoblastic leukaemia, 1980-2001. Leukemia. 2010;24(2):406-18. DOI: 10.1038/leu.2009.256 13. Evans WE, Relling MV, Rodman JH, Crom WR, Boyett JM, Pui CH. Conventional compared with individualized chemotherapy for childhood acute

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Infant acute leukemia with lineage switch at relapse expressing a novel t(4;11)(q21;q23) MLL-AF4 fusion transcript

References 1. De Braekeleer E, Douet-Guilbert N, Le Bris MJ, Basinko A, Morel F, De Braekeleer M. Gene expression profiling of adult t(4;11)(q21;q23)-associated acute lymphoblastic leukemia reveals a different signature from pediatric cases. Anticancer Res. 2012 Sep;32(9):3893-9 2. De Braekeleer M, Morel F, Le Bris MJ, Herry A, Douet-Guilbert N. The MLL gene and translocations involving chromosomal band 11q23 in acute leukemia. Anticancer Res. 2005 May-Jun;25(3B):1931-44 3. Drexler HG, Quentmeier H

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A rare case of acute myeloid leukemia with ARHGEF12 (LARG, 11q23.3) and MAPRE1 (EB1, 20q11.21) fusion gene in an elderly patient

-03-643544 4. Wang Y, Wu N, Liu D, Jin Y. Recurrent Fusion Genes in Leukemia: An Attractive Target for Diagnosis and Treatment. Curr Genomics. 2017;18(5):378-384. DOI: 10.2174/1389202918666170329110349 5. Fu JF, Hsu HC, Shih LY. MLL is fused to EB1 (MAPRE1), which encodes a microtubule-associated protein, in a patient with acute lymphoblastic leukemia. Genes Chromosomes Cancer. 2005;43(2):206-10. DOI: 10.1002/gcc.20174 6. Kourlas PJ, Strout MP, Becknell B, Veronese ML, Croce CM, Theil KS et al. Identification of a gene at 11q23 encoding a guanine nucleotide

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Genetic testing in pediatrics - a narrative essay of challenges and possibilities in Romania

outcome of children with acute lymphoblastic leukemia - experience of IIIrd Paediatric Clinic Timisoara. Rev Romana Med Lab. 2018;26(1):77-85. DOI: 10.1515/rrlm-2017-0029 16. Tripon F, Crauciuc GA, Moldovan VG, Bogliș A, Benedek IJ, Lázár E, et al. Simultaneous FLT3, NPM1 and DNMT3A mutations in adult patients with acute myeloid leukemia - case study. Rev Romana Med Lab. 2019;27(3):245-54. DOI: 10.2478/rrlm-2019-0022 17. Oltean A, Chincesan MI, Marginean O, Horvath E. Myelodysplastic syndrome with myelofibrosis in a 12-year-old patient - A case report. Rev

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Variability of ex-vivo stimulated T-cells secretory profile in healthy subjects

, Azuma E, et al. Intracellular cytokine profile of T cells from children with acute lymphoblastic leukemia. Cancer Immunol Immunother. 2000 Jun;49(3):165-72. DOI: 10.1007/s002620050616 23. Gallego A, Vargas JA, Castejón R, Citores MJ, Rome-ro Y, Millán I, et al. Production of intracellular IL-2, TNF-alpha, and IFN-gamma by T cells in B-CLL. Cytometry B Clin Cytom. 2003Nov;56(1):23.9. DOI: 10.1002/cyto.b.10052 24. Karanikas V, Lodding J, Maino VC, McKenzie IF. Flow cytometric measurement of intracellular cytokines detects immune responses in MUC1

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From influenza infection to anti-ADAMTS13 autoantibodies via cross-reactivity

methylating/histone modifying enzymes: a potential link to childhood acute lymphoblastic leukemia, Int. J. Pediatr. Child Health, 2017, 5, 29-39. Polito A. Polimeno R. Kanduc D. Peptide sharing between Parvovirus B19 and DNA methylating/histone modifying enzymes: a potential link to childhood acute lymphoblastic leukemia Int. J. Pediatr. Child Health 2017 5 29 39 [54] Kanduc, D., Epstein-Barr virus, immunodeficiency, and cancer: a potential crossreactivity connection. Intern. Med. Rev., 2018, 4, 1–17. Kanduc D. Epstein-Barr virus

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In vitro drug sensitivity in canine lymphoma

References 1. Den Boer M.L., Harms D.O., Pieters R., Kazemier K.M., Gobel U., Körholz D., Graubner U., Haas R.J., Jorch N., Spaar H.J., Kaspers G.J., Kamps W.A., Van der Does-Van den Berg A., Van Wering E.R., Veerman A.J., Janka-Schaub G.E.: Patient stratification based on prednisolone-vincristineasparaginase resistance profiles in children with acute lymphoblastic leukemia. J Clin Oncol 2003, 21, 262-3268. 2. Escherich G., Tröger A., Göbel U., Graubner U., Pekrun A., Jorch N., Kaspers G., Zimmermann M., zur Stadt U., Kazemier

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Myelodysplastic syndrome with myelofibrosis in a 12-year-old patient – A case report

lymphoblastic leukaemia: implications for disease biology. Leuk Res. 2006;30:233-239. DOI: 10.1016/j.leukres.2005.06.011 4. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;1145(5):937-51. DOI: 10.1182/blood-2009-03-209262 5. Tefferi A. Pathogenesis of myelofibrosis with myeloid metaplasia. J Clin Oncol. 2005;23(33):8520-30. DOI: 10.1200/JCO.2004

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