Sobrecarga de ferro e estresse oxidativo em pacientes submetidos a transplante de células precursoras hematopoiéticas

Detalhes bibliográficos
Autor(a) principal: Naoum, Flávio Augusto
Data de Publicação: 2006
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da FAMERP
Texto Completo: http://bdtd.famerp.br/handle/tede/235
Resumo: High-dose chemotherapy with hematopoietic stem-cell transplantation (HCT) is a modality of treatment that has been used for an increasing number of diseases. However, the outcome and applicability of HCT are limited by the toxicity and mortality associated with this procedure. It is presumed that iron overload and oxidative stress with free radicals production may be associated with the complications observed after HCT. Objective: Evaluate the onset and evolution of iron overload and oxidative stress at early and late phases of HCT, and correlate this events with clinical characteristics pre and post-transplant. Patients and methods: Laboratorial markers of iron overload (serum iron, transferrin saturation and ferritin) and oxidative stress (uric acid, albumin, superoxide dismutase (SOD) and metaemoglobin) were analyzed in 21 patients undergoing allogeneic or autologous HCT. The parameters were determined before HCT, on day 0, day +14 and at 6 months post-transplant, and the results were correlated with clinical antecedents, engraftment and complications observed after HCT. Results: After high-dose chemotherapy there was a marked increase in all iron overload parameters and a reduction of uric acid and albumin levels, indicating the presence of oxidative stress. Except for ferritin levels, all the parameters that were altered after conditioning regained baseline levels at 6 moths post-HCT. Previous red blood cell transfusions correlated mainly with ferritin levels. Citotoxic treatment before HCT was associated with increased basal levels of all iron parameters and reduced acid uric concentration on day +14. Suppression of hematopoiesis, accessed by engraftment markers, was associated with iron overload (increased levels of serum iron and transferrin saturation) and oxidative stress exacerbation (reduced uric acid and SOD concentrations). Within the group transplanted in remission, patients who developed grades III-IV toxicity had higher baseline levels of iron parameters. Transplant-related mortality was increased in patients with high levels of transferrin saturation on day 0. Conclusion: Iron overload and oxidative stress are acute complications observed after high-dose chemotherapy for HCT that are probably related to delayed hematological recovery and increased morbi-mortality post-transplant. It is suggested that this parameters may be used as markers of engraftment and toxicity after HCT.
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spelling Ruiz, Milton ArturCPF:0000000117http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4797517P6Souza, Dorotéia Rossi SilvaCPF:06048566887SOUZA, Dorotéia Rossi SilvaMattos, Luiz Carlos deCPF:00000000056http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4700585P2&dataRevisao=nullCançado, Rodolfo DelfiniCPF:0000000118http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4777632U3Fabron Junior, AntonioCPF:0000000119http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4792000J0CPF:27249103890http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4739315J8Naoum, Flávio Augusto2016-01-26T12:51:53Z2007-03-282006-08-25NAOUM, Flávio Augusto. Sobrecarga de ferro e estresse oxidativo em pacientes submetidos a transplante de células precursoras hematopoiéticas. 2006. 103 f. Tese (Doutorado em Medicina Interna; Medicina e Ciências Correlatas) - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, 2006.http://bdtd.famerp.br/handle/tede/235High-dose chemotherapy with hematopoietic stem-cell transplantation (HCT) is a modality of treatment that has been used for an increasing number of diseases. However, the outcome and applicability of HCT are limited by the toxicity and mortality associated with this procedure. It is presumed that iron overload and oxidative stress with free radicals production may be associated with the complications observed after HCT. Objective: Evaluate the onset and evolution of iron overload and oxidative stress at early and late phases of HCT, and correlate this events with clinical characteristics pre and post-transplant. Patients and methods: Laboratorial markers of iron overload (serum iron, transferrin saturation and ferritin) and oxidative stress (uric acid, albumin, superoxide dismutase (SOD) and metaemoglobin) were analyzed in 21 patients undergoing allogeneic or autologous HCT. The parameters were determined before HCT, on day 0, day +14 and at 6 months post-transplant, and the results were correlated with clinical antecedents, engraftment and complications observed after HCT. Results: After high-dose chemotherapy there was a marked increase in all iron overload parameters and a reduction of uric acid and albumin levels, indicating the presence of oxidative stress. Except for ferritin levels, all the parameters that were altered after conditioning regained baseline levels at 6 moths post-HCT. Previous red blood cell transfusions correlated mainly with ferritin levels. Citotoxic treatment before HCT was associated with increased basal levels of all iron parameters and reduced acid uric concentration on day +14. Suppression of hematopoiesis, accessed by engraftment markers, was associated with iron overload (increased levels of serum iron and transferrin saturation) and oxidative stress exacerbation (reduced uric acid and SOD concentrations). Within the group transplanted in remission, patients who developed grades III-IV toxicity had higher baseline levels of iron parameters. Transplant-related mortality was increased in patients with high levels of transferrin saturation on day 0. Conclusion: Iron overload and oxidative stress are acute complications observed after high-dose chemotherapy for HCT that are probably related to delayed hematological recovery and increased morbi-mortality post-transplant. It is suggested that this parameters may be used as markers of engraftment and toxicity after HCT.A quimioterapia de altas doses com transplante de células precursoras hematopoiéticas (TCPH) é uma modalidade terapêutica utilizada para um número cada vez maior de doenças. Entretanto o sucesso e a aplicabilidade desse tratamento são limitados pela toxicidade e mortalidade inerentes à quimioterapia de altas doses. Especula-se que a sobrecarga de ferro e o estresse oxidativo com geração de radicais livres possam estar relacionados às complicações observadas no TCPH. Objetivo: Analisar a presença e a evolução da sobrecarga de ferro e do estresse oxidativo nas fases precoce e tardia do TCPH, e correlacioná-los aos dados clínicos pré e pós-transplante. Casuística e método: Parâmetros laboratoriais de sobrecarga de ferro (ferro sérico, saturação da transferrina e ferritina) e estresse oxidativo (ácido úrico, albumina, superóxido dismutase (SOD) e metaemoglobina) foram analisados em 21 pacientes submetidos a TCPH alogênicos e autogênicos. As determinações laboratoriais foram realizadas antes do TCPH, no D0, no D+14 e após 6 meses de transplante, e correlacionadas com as características clínicas dos pacientes, enxertia e complicações observadas após o TCPH. Resultados: Após a quimioterapia de altas doses houve elevação acentuada de todos os parâmetros de sobrecarga de ferro e redução dos valores dos valores de ácido úrico e albumina, indicando presença de estresse oxidativo. Com exceção da ferritina, os parâmetros que se alteraram após o condicionamento retornaram aos valores basais após 6 meses de TCPH. O número de transfusões prévias de concentrados de hemácias se correlacionou principalmente com os valores de ferritina. A realização de quimioterapia prévia ao TCPH foi associada à valores basais elevados do perfil de ferro e redução da concentração de ácido úrico no D+14. A supressão da atividade hematopoiética, analisada por meio dos parâmetros de enxertia, esteve associada à sobrecarga de ferro (elevação do ferro sérico e da saturação da transferrina) e à exacerbação do estresse oxidativo (redução dos valores de ácido úrico e de SOD). Dentre os pacientes transplantados em remissão completa, o perfil de ferro basal fora mais elevado naqueles que desenvolveram toxicidade graus III-IV. A mortalidade precoce relacionada ao transplante foi maior nos pacientes que apresentaram valores elevados de saturação da transferrina no D0. Conclusão: A sobrecarga de ferro e o estresse oxidativo são eventos que ocorrem de forma aguda após a quimioterapia de altas doses para TCPH e estão, aparentemente, relacionados à recuperação hematológica mais demorada e ao aumento da morbi-mortalidade no pós-transplante. Sugere-se que os parâmetros estudados sejam adotados como marcadores de enxertia e de toxicidade pós-TCPH.Made available in DSpace on 2016-01-26T12:51:53Z (GMT). No. of bitstreams: 1 flavioaugustonaoum_tese.pdf: 375547 bytes, checksum: a77630a0cfb1dd1d987a557c2f5c1961 (MD5) Previous issue date: 2006-08-25application/pdfporFaculdade de Medicina de São José do Rio PretoPrograma de Pós-Graduação em Ciências da Saúde::123123::600FAMERPBRMedicina Interna; Medicina e Ciências Correlatas::123123::600Transplante de Medula ÓsseaSobrecarga de FerroEstresse OxidativoCNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::HEMATOLOGIA::123123::600Sobrecarga de ferro e estresse oxidativo em pacientes submetidos a transplante de células precursoras hematopoiéticasinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da FAMERPinstname:Faculdade de Medicina de São José do Rio Preto (FAMERP)instacron:FAMERPORIGINALflavioaugustonaoum_tese.pdfapplication/pdf375547a77630a0cfb1dd1d987a557c2f5c1961MD51http://bdtd.famerp.br/bitstream/tede/235/1/flavioaugustonaoum_tese.pdftede/2352019-02-04 11:06:08.799oai:localhost:tede/235Biblioteca Digital de Teses e Dissertaçõeshttp://bdtd.famerp.br/PUBhttps://bdtd.famerp.br/oai/requestsbdc@famerp.br||joao.junior@famerp.bropendoar:47112019-02-04T13:06:08Biblioteca Digital de Teses e Dissertações da FAMERP - Faculdade de Medicina de São José do Rio Preto (FAMERP)false
dc.title.por.fl_str_mv Sobrecarga de ferro e estresse oxidativo em pacientes submetidos a transplante de células precursoras hematopoiéticas
title Sobrecarga de ferro e estresse oxidativo em pacientes submetidos a transplante de células precursoras hematopoiéticas
spellingShingle Sobrecarga de ferro e estresse oxidativo em pacientes submetidos a transplante de células precursoras hematopoiéticas
Naoum, Flávio Augusto
Transplante de Medula Óssea
Sobrecarga de Ferro
Estresse Oxidativo
CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::HEMATOLOGIA::123123::600
title_short Sobrecarga de ferro e estresse oxidativo em pacientes submetidos a transplante de células precursoras hematopoiéticas
title_full Sobrecarga de ferro e estresse oxidativo em pacientes submetidos a transplante de células precursoras hematopoiéticas
title_fullStr Sobrecarga de ferro e estresse oxidativo em pacientes submetidos a transplante de células precursoras hematopoiéticas
title_full_unstemmed Sobrecarga de ferro e estresse oxidativo em pacientes submetidos a transplante de células precursoras hematopoiéticas
title_sort Sobrecarga de ferro e estresse oxidativo em pacientes submetidos a transplante de células precursoras hematopoiéticas
author Naoum, Flávio Augusto
author_facet Naoum, Flávio Augusto
author_role author
dc.contributor.advisor1.fl_str_mv Ruiz, Milton Artur
dc.contributor.advisor1ID.fl_str_mv CPF:0000000117
dc.contributor.advisor1Lattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4797517P6
dc.contributor.referee1.fl_str_mv Souza, Dorotéia Rossi Silva
dc.contributor.referee1ID.fl_str_mv CPF:06048566887
dc.contributor.referee1Lattes.fl_str_mv SOUZA, Dorotéia Rossi Silva
dc.contributor.referee2.fl_str_mv Mattos, Luiz Carlos de
dc.contributor.referee2ID.fl_str_mv CPF:00000000056
dc.contributor.referee2Lattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4700585P2&dataRevisao=null
dc.contributor.referee3.fl_str_mv Cançado, Rodolfo Delfini
dc.contributor.referee3ID.fl_str_mv CPF:0000000118
dc.contributor.referee3Lattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4777632U3
dc.contributor.referee4.fl_str_mv Fabron Junior, Antonio
dc.contributor.referee4ID.fl_str_mv CPF:0000000119
dc.contributor.referee4Lattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4792000J0
dc.contributor.authorID.fl_str_mv CPF:27249103890
dc.contributor.authorLattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4739315J8
dc.contributor.author.fl_str_mv Naoum, Flávio Augusto
contributor_str_mv Ruiz, Milton Artur
Souza, Dorotéia Rossi Silva
Mattos, Luiz Carlos de
Cançado, Rodolfo Delfini
Fabron Junior, Antonio
dc.subject.por.fl_str_mv Transplante de Medula Óssea
Sobrecarga de Ferro
Estresse Oxidativo
topic Transplante de Medula Óssea
Sobrecarga de Ferro
Estresse Oxidativo
CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::HEMATOLOGIA::123123::600
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::HEMATOLOGIA::123123::600
description High-dose chemotherapy with hematopoietic stem-cell transplantation (HCT) is a modality of treatment that has been used for an increasing number of diseases. However, the outcome and applicability of HCT are limited by the toxicity and mortality associated with this procedure. It is presumed that iron overload and oxidative stress with free radicals production may be associated with the complications observed after HCT. Objective: Evaluate the onset and evolution of iron overload and oxidative stress at early and late phases of HCT, and correlate this events with clinical characteristics pre and post-transplant. Patients and methods: Laboratorial markers of iron overload (serum iron, transferrin saturation and ferritin) and oxidative stress (uric acid, albumin, superoxide dismutase (SOD) and metaemoglobin) were analyzed in 21 patients undergoing allogeneic or autologous HCT. The parameters were determined before HCT, on day 0, day +14 and at 6 months post-transplant, and the results were correlated with clinical antecedents, engraftment and complications observed after HCT. Results: After high-dose chemotherapy there was a marked increase in all iron overload parameters and a reduction of uric acid and albumin levels, indicating the presence of oxidative stress. Except for ferritin levels, all the parameters that were altered after conditioning regained baseline levels at 6 moths post-HCT. Previous red blood cell transfusions correlated mainly with ferritin levels. Citotoxic treatment before HCT was associated with increased basal levels of all iron parameters and reduced acid uric concentration on day +14. Suppression of hematopoiesis, accessed by engraftment markers, was associated with iron overload (increased levels of serum iron and transferrin saturation) and oxidative stress exacerbation (reduced uric acid and SOD concentrations). Within the group transplanted in remission, patients who developed grades III-IV toxicity had higher baseline levels of iron parameters. Transplant-related mortality was increased in patients with high levels of transferrin saturation on day 0. Conclusion: Iron overload and oxidative stress are acute complications observed after high-dose chemotherapy for HCT that are probably related to delayed hematological recovery and increased morbi-mortality post-transplant. It is suggested that this parameters may be used as markers of engraftment and toxicity after HCT.
publishDate 2006
dc.date.issued.fl_str_mv 2006-08-25
dc.date.available.fl_str_mv 2007-03-28
dc.date.accessioned.fl_str_mv 2016-01-26T12:51:53Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
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dc.identifier.citation.fl_str_mv NAOUM, Flávio Augusto. Sobrecarga de ferro e estresse oxidativo em pacientes submetidos a transplante de células precursoras hematopoiéticas. 2006. 103 f. Tese (Doutorado em Medicina Interna; Medicina e Ciências Correlatas) - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, 2006.
dc.identifier.uri.fl_str_mv http://bdtd.famerp.br/handle/tede/235
identifier_str_mv NAOUM, Flávio Augusto. Sobrecarga de ferro e estresse oxidativo em pacientes submetidos a transplante de células precursoras hematopoiéticas. 2006. 103 f. Tese (Doutorado em Medicina Interna; Medicina e Ciências Correlatas) - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, 2006.
url http://bdtd.famerp.br/handle/tede/235
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dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Ciências da Saúde::123123::600
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dc.publisher.department.fl_str_mv Medicina Interna; Medicina e Ciências Correlatas::123123::600
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