DSpace logo

Use este identificador para citar ou linkar para este item: http://repositorioinstitucional.uea.edu.br//handle/riuea/4115
Registro completo de metadados
Campo DCValorIdioma
dc.contributor.authorCarvalho , Maria do Perpetuo Socorro Sampaio-
dc.date.available2022-08-09-
dc.date.available2022-08-11T16:50:33Z-
dc.date.issued2015-11-16-
dc.identifier.urihttp://repositorioinstitucional.uea.edu.br//handle/riuea/4115-
dc.description.abstractCurrent proposals treatment of children and adolescents with acute lymphoblastic leukemia enable increased survival, increase the chances of cure of patients and seek to reduce late effects related to therapy and the Brazilian Group of Treatment of Leukemia Acute Lymphoblastic of Children and Adolescents - GBTLI proposes regimens categorized by prognostic criteria for relapse risk of this condition. These patients have immunological profile changed by the disease itself and held by therapy which can contribute to the response and complications during treatment. The study aimed to describe the cellular immune response profile of cytokines, chemokines and identify possible immune biomarkers according to the treatment-risk group with GBTLI LLA-2009 protocol in patients with ALL aged zero to minor 18 years during induction therapy. The methodology used was not experimental, longitudinal, prospective cohort. Patients were stratified by risk group and analyzed during induction therapy in four stages: the diagnosis (D0), the eighth day (D8), the fifteenth day (D15) and thirty-fifth day (D35). The control group performed only one evaluation. The immune response was characterized by analysis of total lymphocytes, T lymphocytes (LT), LT CD4+, LT CD8+, NK cells, NKT cells and Treg lymphocytes CD4+/CD25+/FoxP3+) and serum cytokines Th1, Th2, Treg and Th17 and serum chemokines MCP-1, RANTES, IL-8, IP-10 and MIG by flow cytometry. In the study it was observed that the diagnosis LT-were reduced in the first fifteen days of induction. IL-2, IFN-γ and IL-4 were reduced to their production, but not significant. The CD4+ and CD8+ were increased throughout the induction. Treg lymphocytes increased only on D15 and D35. NK cells decreased at D0, D15 and D35, and NKT cell only on D0 and in particular RA group. IL-6 was increased in D0 and IL-10 at D0 and D8. The TNF-α presented itself decreased throughout the induction. RANTES was decreased in D0, D15 and D8 and MIG decreased from D8 until the end of induction. MCP-1 decreased the D15 and IL-8 increased in RH group in D35. In interactions networks, Treg lymphocytes on D0 interacted with MCP-1, MIG and IP-10 and IL-10 with IL-8, MCP-1 and MIG and lost their interactions in D35. These results suggest that patients with ALL at diagnosis have immune dysregulation. The predominance of interactions immunoregulatory response by IL-10 and Treg lymphocytes with cytokines / chemokines may indicate a decrease or loss of its action at the end of induction, with a predominance of the inflammatory response, which suggests tumor control and bone marrow recoverypt_BR
dc.languageporpt_BR
dc.publisherUniversidade do Estado do Amazonaspt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectLeucemia linfoblástica agudapt_BR
dc.subjectPerfil celular.pt_BR
dc.subjectCitocinas séricaspt_BR
dc.subjectQuimiocinas séricapt_BR
dc.subjectBiomarcadores imunept_BR
dc.subjectacute lymphoblastic leukemiapt_BR
dc.titleEstudo do perfil imunológico em crianças e adolescentes com Leucemia Linfoblástica Aguda no Amazonaspt_BR
dc.title.alternativeStudy of the immunological profile in children and adolescents with Acute Lymphoblastic Leukemia in Amazonaspt_BR
dc.typeDissertaçãopt_BR
dc.date.accessioned2022-08-11T16:50:33Z-
dc.contributor.advisor-co1Fraiji , Nelson Abrahim-
dc.contributor.advisor-co1Latteshttp://lattes.cnpq.br/5204063085335824pt_BR
dc.contributor.advisor1Marie, Adriana Malheiro Alle-
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/2627415957053194pt_BR
dc.contributor.referee1Marie, Adriana Malheiro Alle-
dc.contributor.referee1Latteshttp://lattes.cnpq.br/2627415957053194pt_BR
dc.contributor.referee2Sadahiro, Aya-
dc.contributor.referee2Latteshttp://lattes.cnpq.br/8658798733544812pt_BR
dc.contributor.referee3Passos, Luiz Fernando de Souza-
dc.contributor.referee3Latteshttp://lattes.cnpq.br/4230544141006141pt_BR
dc.creator.Latteshttp://lattes.cnpq.br/6633894737276791pt_BR
dc.description.resumoAs propostas atuais de tratamento das crianças e adolescentes com leucemia linfoblástica aguda possibilitam o aumento de sobrevida, elevam as chances de cura dos pacientes e buscam reduzir os efeitos tardios relacionados à terapia e o Grupo Brasileiro de Tratamento das Leucemias Linfoblástica Aguda da Criança e do Adolescente - GBTLI, propõe esquemas terapêuticos categorizados por critérios prognósticos de risco de recidiva desta patologia. Estes pacientes tem o perfil imunológico alterado pela própria doença e pela terapia realizada o que pode contribuir para a resposta e complicações durante o tratamento. O estudo teve como objetivo descrever a resposta imune celular, perfil de citocinas, quimiocinas e pesquisar possíveis biomarcadores imunes de acordo com o grupo de risco de tratamento com o protocolo GBTLI LLA-2009, em pacientes com LLA na faixa etária de zero a menor de 18 anos durante a terapia de indução. A metodologia usada foi a não experimental, longitudinal, de coorte e prospectivo. Participaram deste estudo, 29 pacientes que foram estratificados por grupo de risco: Alto Risco (AR), Baixo Risco (BR), LLA T, Philadelfia (Ph⁺ ) e Lactente e analisados durante a terapia de indução em quatro etapas: ao diagnóstico (D0), oitavo dia (D8), décimo quinto dia (D15) e trigésimo quinto dia (D35). O Grupo Controle, contou com 28 participantes e realizou apenas uma avaliação. A resposta imune foi caracterizada pela análise dos linfócitos totais, linfócitos T (LT), LT CD4⁺, LT CD8⁺, células NK, células NKT e linfócitos Treg CD4⁺/CD25⁺/FoxP3⁺), assim como as citocinas séricas Th1, Th2, Th17 e Treg e quimiocinas séricas MCP-1, RANTES, IL-8, MIG e IP-10 através da técnica de citometria de fluxo. No estudo observou-se ao diagnóstico que os LT encontravam-se diminuídos nos primeiros quinze dias da indução. A IL-2, IFN-γ e IL-4 estavam com sua produção diminuída, porém não significantes. Os LT CD4+ e LT CD8+ estavam aumentados durante toda a indução. Os linfócitos Treg aumentados apenas no D15 e D35. As células NK diminuídas no D0, D15 e D35, e a célula NKT somente no D0 e em especial no grupo de AR. A IL-6 estava aumentada no D0 e a IL-10 no D0 e D8. A TNF-α apresentou-se diminuída em toda a indução. RANTES estava diminuída no D0, D8 e D15 e MIG diminuiu a partir do D8 até o final da indução. MCP-1 diminuiu no D15 e IL-8 aumentou no grupo de AR no D35. Nas redes de interações, os linfócitos Treg no D0 interagiram com MCP-1, MIG e IP-10 e a IL-10 com a IL-8, MCP-1 e MIG e perderam suas interações no D35. Estes resultados demonstram que os pacientes com LLA apresentam desregulação imune ao diagnóstico. O predomínio de interações da resposta imunorreguladora pela IL-10 e linfócito Treg com citocinas/quimiocinas inflamatórias podem indicar a diminuição ou perda de sua ação ao final da indução, ou seja no D35, havendo predomínio da resposta inflamatória, o que sugere controle tumoral e recuperação medularpt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.programPPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIApt_BR
dc.relation.references1. Elman I, Silva MEMP. Crianças Portadoras de Leucemia Linfóide Aguda: Análise dos Limiares de Detecção dos Gostos Básicos. Revista Brasileira de Cancerologia 2007; 53(3): 297-303. 2. Ek T, Mellander L, Hahn-Zoric M, Abrahamsson J. Intensive Treatment for Childhood Acute Lymphoblastic Leukemia Reduces Immune Responses to Diphtheria, Tetanus, and Haemophilus influenzae Type b. J Pediatr Hematol Oncol 2004; 26: 727-734. 3. Hirzel AC, Cotrell A, Gasparini R, Sriganeshan V. Precursor B-Cell Acute Lymphoblastic Leukemia/Lymphoma with L3 Morphology, Philadelphia Chromosome, MYC Gene Translocation, and Coexpression of TdT and Surface Light Chains: A Case Report. Case Rep Pathol. 2013; 2013: 679892. 4. Mullighan CG. Molecular genetics of B-precursor acute lymphoblastic leukemia. J Clin Invest. 2012; 122(10): 3407-3415. 5. Kampen KR. The discovery and early understanding of leukemia. Leukemia 2012; 36(1): 6-13. 6. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC: lYON, 2008. 7. GLOBOCAN (International Agency for research on cancer). World Health Organization. (WHO). Estimated Cancer Incidence, Mortality and Prevalence worldwide in 2012. Disponível em: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Acessado em 12 de agosto de 2015. 8. Chiaretti S, Zini G, Bassan R. Diagnosis and Subclassification of Acute Lymphoblastic Leukemia. Mediterr J Hematol Infect Dis 2014, 6(1): e2014073. xcv 95 9. Brasil, Ministério da Saúde, Instituto Nacional do Câncer (INCA). Estimativas do Caâcer no Brasil (2014): Síntese de Resultados. Disponível em: http://www1.inca.gov.br/tumores_infantis/pdf/9_resultados_comentarios_incidencia_por _tipo_de_cancer.pdf. Acessado em 28 de Junho de 2015. 10. Parkin DM, Stiller CA, Draper GJ, Bieber CA. The international incidence of childhood cancer. Int J Cancer. 1988; 42(4): 511-520. 11. National Cancer Institute (NCI). Childhood Acute Lymphoblastic Leukemia Treatment for health professionals (PDQ®): General Information About Childhood Acute Lymphoblastic Leukemia (ALL). Disponível em: http://www.cancer.gov/types/leukemia/hp/child-all- treatment-pdq#link/_7_toc. Acessado em: 28 de Junho de 2015. 12. Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, Reaman GH, Carroll WL. Improved Survival for Children and Adolescents With Acute Lymphoblastic Leukemia Between 1990 and 2005: A Report From the Children's Oncology Group. J Clin Oncol. 30(14):1663-1669. 2012. 13. Bathia S, Robinson L. Epidemiology of leukemia in childhood. In: Nathan DG, Orkin SH, Ginsburg D, Look AT, editors. Nathan and Oski’s Hematology of Infancy and childhood. 6th ed. Philadelphia: Saunders; 2003. 14. Hosoi Y. Radiation carcinogenesis. Gan To Kagaku Ryoho. 2013; 40(11): 1446-1450. 15. Ellinghaus E, Stanulla M, Richter G, Ellinghaus D, 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. Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia. Leukemia 2012; 26(5): 902-909. xcvi 96 16. Wiemels J. Perspectives on the Causes of Childhood Leukemia. Chem Biol Interact. 2012; 196(3): 59-67. 17. Duramad P, Tager IB, Holland NT. Cytokines and other immunological biomarkers in children’s environmental health studies. Toxicol Lett. 2007; 172(1-2): 48-59. 18. Bartram CR, Schrauder A, Köhler R, Schrappe M. Acute lymphoblastic leukemia in children: treatment planning via minimal residual disease assessment. Dtsch Arztebl Int. 2012; 109(40): 652-658. 19. Braga JAP, Tone LG, Loggetto SR. Hematologia para a Pediatra. São Paulo: Atheneu, 2007. 20. Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 5th ed, USA: Elsevier, 2011. 21. McGregor S, McNeer J, Gurbuxani S. World Health Organization classification: the role of the hematopathology laboratory in the diagnosis and management of acute lymphoblastic leukemia. Semin Diagn Pathol. 2012; 29(1): 2-11. 22. Van Dongen JJ. EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia. 2012; 26(9): 1908-1975. 23. Wu CP, Qing X, Wu CY, Zhu H, Zhou HY. Immunophenotype and increased presence of CD4⁺CD25⁺ regulatory T cells in patients with acute lymphoblastic leukemia. Oncol Lett. 2012; 3(2): 421-424. 24. Inaba H, Greaves M, Mullighan CG. Acute lymphoblastic leukaemia. Lancet. 2013; 381(9881): 62187-62194. 25. Coustan-Smith E, Campana D. Immunologic minimal residual disease detection in lymphoblastic leukemia: comparative approach to molecular testing. Best Pract Res Clin Haematol. 2010; 23(3): 347-358. xcvii 97 26. Garcia AV, Alobeid B, Traina JM, Chen SS, Weiner MA, Middlesworth W. Isolated primary testicular B lymphoblastic lymphoma: an unusual presentation. J Pediatr Hematol Oncol. 2013; 35(2): e88-e90. 27. Pui CH, Mullighan CG, Evans WE, Relling MV. Pediatric acute lymphoblastic leukemia: where are we going and how do we get there? Blood. 2012; 120(6): 1165-1174. 28. Brandalise SR, Pinheiro VR, LEE MLM. Protocolo de Tratamento da Leucemia Linfoblástica Aguda da Criança e do Adolescente- GBTLI, Brasil, 2009. 29. Shah A, Coleman MP. Increasing incidence of childhood leukemia: a controversy re- examined. Br J Cancer. 2007; 8, 97 (7): 1009-1012. 30. Cooper SL, Brown PA. Treatment of Pediatric Acute Lymphoblastic Leukemia. Pediatr Clin North Am. 2015; 62(1): 61-73. 31. Feuerecker M, Mayer W, Kaufmann I, Gruber M, Muckenthaler F, Yi B, Salam AP, Briegel J, Schelling G, Thiel M, Choukèr A. A corticoid-sensitive cytokine release assay for monitoring stress-mediated immune modulation. Clin Exp Immunol. 2013; 172(2): 290-299. 32. Cruvinel WM, Mesquita D Jr, Araújo JA, Catelan TT, de Souza AW, da Silva NP, Andrade LE. Immune system - part I. Fundamentals of innate immunity with emphasis on molecular and cellular mechanisms of inflammatory response. Rev Bras Reumatol. 2010; 50(4): 434- 461. 33. Baltimore D, Boldin MP, O'Connell RM, Rao DS, Taganov KD. MicroRNAs: new regulators of immune cell development and function. Nature Immunology. 2008; 9: 839 – 845. 34. Eisenbarth SC, Flavell RA. Innate instruction of adaptive immunity revisited: the inflammasome. EMBO Mol Med. 2009; 1(2): 92-98. xcvii i 98 35. Capitini CM, Chisti AA, Mackall CL. Modulating T cell Homeostasis with IL-7: Preclinical and Clinical Studies. Journal of Internal Medicine. 2009; 266(2): 141-153. 36. Souza AWS, Mesquita-Júnior D, Araújo JAP, Catelan TTT, Cruvinel WM, Andrade LEC, Silva NP. The delicate balance of the immune system between tolerance and autoimmunity. Bras J Rheumatol 2010; 50(6): 665-694. 37. Dayanidhi Raman D, Paige J. Baugher PJ, Yee Mon Thu YM, Ann Richmond A. Role of chemokines in tumor growth. Cancer Lett. 2007; 256(2): 137-165. 38. Zhang, XL, Komada Y, Chipeta J, Li QS, Inaba H, Azuma E, Yamamoto H, Sakurai M. Intracellular cytokine profile of T cells from children with acute lymphoblastic leukemia. Cancer Immunol Immunother 2000; 49:165-172. 39. Mesquita Júnior D, Araújo JA, Catelan TT, Souza AW, Cruvinel Wde M, Andrade LE, Silva NP. Immune system - part II: basis of the immunological response mediated by T and B lymphocytes. Rev Bras Reumatol. 2010; 50(5): 552-580. 40. Machado PRL, Araújo MIAS, Carvalho L, Carvalho EM. Immune response mechanisms to infections. An bras Dermatol. 2004; 79(6): 647-664. 41. Bhattacharya K, Chandra S, Mandal C. Critical stoichiometric ratio of CD4(+) CD25(+) FoxP3(+) regulatory T cells and CD4(+) CD25(-) responder T cells influence immunosuppression in patients with B-cell acute lymphoblastic leukaemia. Immunology. 2014; 142(1): 124-139. 42. Farnault L, Sanchez C, Baier C, Le Treut T, Costello RT. Hematological malignancies escape from NK cell innate immune surveillance: mechanisms and therapeutic implications. Clin Dev Immunol. 2012; 2012: 421702. 43. Shigeru S, Akitosh NJ, Tomoko S. Th1/Th2/Th17 and Regulatory T-Cell Paradigm in Pregnancy. American Journal of Reproductive Immunology. 2010; 63(6): 601-610. xcix 99 44. Haining WN, Neuberg DS, Keczkemethy HL, Evans JW, Rivoli S, Gelman R, Rosenblatt HM, Shearer WT, Guenaga J, Douek DC, Silverman LB, Sallan SE, Guinan EC, Nadler LM. Antigen-specific T-cell memory is preserved in children treated for acute lymphoblastic leukemia. Blood. 2005; 106(5): 1749-1754. 45. Roy I, Evans DB, Dwinell MB. Chemokines and chemokine receptors: Update on utility and challenges for the clinician. Surgery. 2014; 155(6): 961-973. 46. Stelmaszczyk-Emmel A, Kopatys A, Górska E, Głodkowska-Mrówka E, Demkow U. The usefulness of flow cytometric analysis of cytokines in peripheral blood and bone marrow plasma. Postepy Hig Med Dosw. 2013; 67: 879-886. 47. Cheon H, Borden EC, Stark GR. Interferons and their stimulated genes in the tumor microenvironment. Semin Oncol. 2014; 41(2): 156-173. 48. Maraninchi D, Vey N, Viens P, Stoppa AM, Archimbaud E, Attal M, Baume D, Bouabdallah R, Demeoq F, Fleury J, Michallet M, Olive D, Reiffers J, Sainty D, Tabilio A, Tiberghien P, Brandely M, Hercend T, Blaise D. A phase II study of interleukin-2 in 49 patients with relapsed or refractory acute leukemia. Leuk Lymphoma. 1998; 31(3-4): 343- 349. 49. Pels E. Comparison of saliva interleukin‑2 concentration to the condition of gums in children with acute lymphoblastic leukaemia during anti‑tumour treatment. Cancer Chemother Pharmacol. 2015; 76(1): 205-210. 50. Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med. 2006; 354(6): 610-621. 51. Vela M, Aris M, Llorente M, Garcia-Sanz JA, Kremer L. Chemokine receptor-specific antibodies in cancer immunotherapy: achievements and challenges. Front Immunol. 2015; 6:12. 52. Yung SC, Murphy PM. Antimicrobial chemokines. Front Immunol. 2012; 3: 276. c 100 53. Olson TS, Ley K. Chemokines and chemokine receptors in leukocyte trafficking. Am J Physiol Regul Integr Comp Physiol. 2002; 283(1): R7-28. 54. Yotnda P, Mintzb P, Grigoriadou K, Lemonnier F, Vilmer E, Langlade-Demoyen P. Analysis of T-cell defects in the specific immune response against acute lymphoblastic leukemia cells. Exp Hematol. 1999; 27(9): 1375-1383. 55. Ek T, Mellander L, Andersson B, Abrahamsson J. Immune reconstitution after childhood acute lymphoblastic leukemia is most severely affected in the high risk group. Pediatr Blood Cancer. 2005; 44(5): 461-468. 56. Ek T, Josefson M, Abrahamsson J. Multivariate Analysis of the relation between immune dysfunction and treatment intensity in children with acute lymphoblastic leukemia. Pediatric Blood Cancer. 2011; 56(7): 1078-1087. 57. Hulley SB, Cumming SR, Browner WS, Grady DG, Hearst NB, Newman TB. Delineando a Pesquisa Clínica: uma abordagem epidemiológica. 2th ed. Porto Alegre: Artmed, 2003. 58. Sousa DWL, Ferreira FVA, Félix FHC, Lopes MVO. Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival. Rev Bras Hematol Hemoter. 2015; 37(4): 223-229. 59. Luczyński W, Stasiak-Barmuta A, Krawczuk-Rybak M, Malinowska I. Assessment of selected co-stimulatory, adhesion and activatory molecules and cytokines of Th(1)/Th(2) balance in acute lymphoblastic leukemia in children. Arch Immunol Ther Exp (Warsz). 2005; 53(4): 357-363. 60. Borim LNB, Ruiz MA, Conte ACF, Camargo B. Estado nutricional como fator prognóstico em crianças portadoras de Leucemia Linfocítica Aguda. Rev. Bras. Hematol. Hemoter. 2000; 22 (1): 47-54. 61. Wiemels J. Perspectives on the causes of childhood leukemia. Chem Biol Interact. 2012; 196(3):59-67. ci 101 62. Lustfeld I, Altvater B, Ahlmann M, Ligges S, Brinkrolf P, Rosemann A, Moericke A, Rossig C. High proportions of CD4⁺ T cells among residual bone marrow T cells in childhood acute lymphoblastic leukemia are associated with favorable early responses. Acta Haematol. 2014; 131(1): 28-36. 63. Vasconcellos JF, Laranjeira AB, Leal PC, Bhasin MK, Zenatti PP, Nunes RJ, Yunes RA, Nowill AE, Libermann TA, Zerbini LF, Yunes JA. Induces Cell Death and Cell Cycle Arrest in Acute Lymphoblastic Leukemia Cells through the Activation of GLIPR1. PLoS One. 2015; 10(8): e0134783pt_BR
dc.publisher.initialsUEApt_BR
Aparece nas coleções:DISSERTAÇÃO - PPCAH Programa de Pós-Graduação em Ciências Aplicadas à Hematologia

Arquivos associados a este item:
Arquivo Descrição TamanhoFormato 
Estudo do perfil imunológico em crianças e adolescentes com Leucemia Linfoblástica Aguda no Amazonas.pdf4,44 MBAdobe PDFVisualizar/Abrir
Mostrar registro simples do item Visualizar estatísticas


Os itens no repositório estão protegidos por copyright, com todos os direitos reservados, salvo quando é indicado o contrário.