Avaliação do uso de inibidores de tirosina quinase em pacientes com leucemia mielóide crônica
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/18069 |
Resumo: | Chronic myeloid leukemia (CML) results from the clonal proliferation of a hematopoietic stem cell representing approximately 15-20% of all cases of leukemia. It is characterized by the presence of the Philadelphia chromosome (Ph), which is the result of the reciprocal translocation between chromosomes 9 and 22. The molecular consequence of translocation is the formation of a hybrid gene, BCR-ABL, encoding a chimeric protein with an intense and dysregulated tyrosine kinase activity, thereby, providing the phenotype of the disease. Over the years, there have been several therapeutic landmarks in the treatment of CML, from busulfan and hydroxyurea until the advent of allogeneic Hematopoietic Stem Cell Transplantation (HSCT) and alpha-interferon. Imatinib mesylate, the first selective tyrosine kinase inhibitor, has been approved by regulatory authorities in 2001 and since that revolutionized the treatment of CML, producing the best therapeutic effects already achieved, except for the HSCT. The excellent clinical results with this drug turned it into the treatment of choice for newly diagnosed patients. Tyrosine kinase second generation inhibitors, such as nilotinib and dasatinib, have been developed having a higher power in order to decrease the chance of disease resistance and expand treatment further options. Presently these drugs are more specific and effective because they are able to trigger a response to the hematological, cytogenetic and molecular level, allowing the patient to have an overall survival practically equal to the general population as well as a quality of life. This cohort study does a retrospective by analyzing medical records of patients with CML treated with tyrosine kinase inhibitors at the University Hospital of Santa Maria (UHSM), attended by the Unified Health System (UHS), describes the epidemiology of this disease in the institution, its evolution in terms of hematologic responses, cytogenetic and molecular, overall survival (OS), progression-free survival (PFS), event-free survival (EFS) and more frequent adverse effects. 98 patients were included, 88.8% in chronic phase, with a mean age of 47.36 years and 58.2% of them were men. About the adverse effects, the most frequent ones were the cramp, myalgia rash and 20%, 15%, 14% respectively. Twelve patients had additional cytogenetic changes to the Ph chromosome, and 50% of these changes were related to worsening of the disease. The HCR was achieved by 91.88%, 84% and 58.33% of patients using imatinib, Dasatinib and Nilotinib respectively. Molecular response was obtained by 78.55% of patients treated with Imatinib, 72% with Dasatinib and 58.7% with Nilotinib. The probability of OS was 95% for 60 months, while PFS and EFS, in the same period, was 85.4% and 69.4% respectively. Patients treated with tyrosine kinase inhibitors in HUSM showed a high frequency of hematological and molecular responses, PFS and OS similar to those described in the world's literature, justifying the investment made by SUS in the purchase of this product. |
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2019-08-29T13:32:31Z2019-08-29T13:32:31Z2016-08-26http://repositorio.ufsm.br/handle/1/18069Chronic myeloid leukemia (CML) results from the clonal proliferation of a hematopoietic stem cell representing approximately 15-20% of all cases of leukemia. It is characterized by the presence of the Philadelphia chromosome (Ph), which is the result of the reciprocal translocation between chromosomes 9 and 22. The molecular consequence of translocation is the formation of a hybrid gene, BCR-ABL, encoding a chimeric protein with an intense and dysregulated tyrosine kinase activity, thereby, providing the phenotype of the disease. Over the years, there have been several therapeutic landmarks in the treatment of CML, from busulfan and hydroxyurea until the advent of allogeneic Hematopoietic Stem Cell Transplantation (HSCT) and alpha-interferon. Imatinib mesylate, the first selective tyrosine kinase inhibitor, has been approved by regulatory authorities in 2001 and since that revolutionized the treatment of CML, producing the best therapeutic effects already achieved, except for the HSCT. The excellent clinical results with this drug turned it into the treatment of choice for newly diagnosed patients. Tyrosine kinase second generation inhibitors, such as nilotinib and dasatinib, have been developed having a higher power in order to decrease the chance of disease resistance and expand treatment further options. Presently these drugs are more specific and effective because they are able to trigger a response to the hematological, cytogenetic and molecular level, allowing the patient to have an overall survival practically equal to the general population as well as a quality of life. This cohort study does a retrospective by analyzing medical records of patients with CML treated with tyrosine kinase inhibitors at the University Hospital of Santa Maria (UHSM), attended by the Unified Health System (UHS), describes the epidemiology of this disease in the institution, its evolution in terms of hematologic responses, cytogenetic and molecular, overall survival (OS), progression-free survival (PFS), event-free survival (EFS) and more frequent adverse effects. 98 patients were included, 88.8% in chronic phase, with a mean age of 47.36 years and 58.2% of them were men. About the adverse effects, the most frequent ones were the cramp, myalgia rash and 20%, 15%, 14% respectively. Twelve patients had additional cytogenetic changes to the Ph chromosome, and 50% of these changes were related to worsening of the disease. The HCR was achieved by 91.88%, 84% and 58.33% of patients using imatinib, Dasatinib and Nilotinib respectively. Molecular response was obtained by 78.55% of patients treated with Imatinib, 72% with Dasatinib and 58.7% with Nilotinib. The probability of OS was 95% for 60 months, while PFS and EFS, in the same period, was 85.4% and 69.4% respectively. Patients treated with tyrosine kinase inhibitors in HUSM showed a high frequency of hematological and molecular responses, PFS and OS similar to those described in the world's literature, justifying the investment made by SUS in the purchase of this product.A Leucemia Mieloide Crônica (LMC) é resultante da proliferação clonal de uma célula tronco hematopoética representando aproximadamente 15-20% dos casos de leucemia. É caracterizada pela presença do cromossomo Philadelphia (Ph), que é o resultado da translocação recíproca entre os cromossomos 9 e 22. A consequência molecular desta translocação é a formação de um gene híbrido BCR-ABL, que codifica uma proteína quimérica com atividade tirosina quinase intensa e desregulada conferindo assim o fenótipo da doença. Ao longo dos anos, houve vários marcos terapêuticos no tratamento da LMC, desde bussulfan e hidroxiureia até o advento do transplante alogênico de células tronco hematopoéticas (TCTH) e alfa interferon. O mesilato de imatinibe (MI), o primeiro inibidor seletivo da tirosina quinase, foi aprovado pelas autoridades regulatórias em 2001 e, a partir daí, revolucionou o tratamento da LMC, produzindo os melhores efeitos terapêuticos já alcançados, exceto pelo TCTH. Os excelentes resultados clínicos com este medicamento o tornaram o tratamento escolhido para pacientes recém-diagnosticados. Inibidores de tirosina quinase de segunda geração, como o dasatinibe e o nilotinibe, foram desenvolvidos apresentando maior potência com a finalidade de diminuir a chance de resistência à doença e expandir ainda mais as opções terapêuticas. No presente, estes fármacos são os mais específicos e efetivos, pois são capazes de desencadear uma resposta a nível hematológico, citogenético e molecular, permitindo que o paciente tenha uma sobrevida global praticamente igual à da população em geral, além de qualidade de vida. Este estudo de coorte faz uma retrospectiva através da análise de prontuários dos pacientes com LMC em tratamento com Inibidores da Tirosina Quinase no Hospital Universitário de Santa Maria (HUSM), atendidos pelo Sistema Único de Saúde (SUS) e que tiveram suas respostas hematológicas, citogenéticas e moleculares monitoradas. Os objetivos foram descrever a epidemiologia da LMC na instituição, sua evolução quanto às respostas hematológicas, citogenéticas e moleculares, sobrevida global (SG), sobrevida livre de progressão (SLP), sobrevida livre de eventos (SLE) e efeitos adversos mais frequentes. Foram incluídos 98 pacientes, 88,8% em fase crônica, com idade média de 47,36 anos e 58,2% eram homens. Quanto aos efeitos adversos, os mais frequentes foram cãibra, mialgia e rash com 20%, 15% e 14% respectivamente. Doze pacientes tiveram alterações citogenéticas adicionais ao cromossomo Ph, destas alterações, e 50% estavam relacionadas com a agudização da doença. A resposta hematológica completa (RHC) foi alcançada por 91,88%, 84% e 58,33% dos pacientes que usaram MI, Dasatinibe e Nilotinibe respectivamente. Resposta molecular foi obtida por 78,55% dos pacientes tratados com MI, 72% com Dasatinibe e 58,7% com Nilotinibe. A probabilidade de SG foi de 95% em 60 meses, enquanto a SLP e SLE, no mesmo período, foi de 85,4% e 69,4% respectivamente. Os pacientes tratados com inibidores da tirosina quinase no HUSM, apresentaram elevada frequência de respostas hematológicas e moleculares, SLP e SG semelhantes às descritas na literatura mundial, justificando o investimento feito pelo SUS na aquisição deste medicamento.porUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em Ciências FarmacêuticasUFSMBrasilAnálises Clínicas e ToxicológicasAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessLeucemia mieloide crônicaInibidores tirosina quinaseRespostaEfetividadeChronic myeloid leukemiaTyrosine kinase inhibitorsResponseEffectivinessCNPQ::CIENCIAS DA SAUDE::FARMACIAAvaliação do uso de inibidores de tirosina quinase em pacientes com leucemia mielóide crônicaEvaluation of tyrosine kinase inhibitors for use in patients with chronic myeloid leukemiainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisSilva, José Edson Paz dahttp://lattes.cnpq.br/1177504021154172Cóser, Virgínia Mariahttp://lattes.cnpq.br/4601008307298787Oliveira, Daniele Carvalho dehttp://lattes.cnpq.br/4817827751698191Duarte, Marta Maria Medeiros Frescurahttp://lattes.cnpq.br/6277584896102052http://lattes.cnpq.br/7757176869080085Goulart, Valéria Pereira201000000000600f31cbb2c-a6b3-42b5-99ec-4f7ceeff6149239f6aa8-673e-439f-a089-2f1ad92d074845fd1a17-92a3-40f6-a132-468542b69d104ca8dea0-e54c-432c-9fde-f3f307c4dbb7558a0333-9455-4f48-b3ef-9e36524ab97freponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMLICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv |
Avaliação do uso de inibidores de tirosina quinase em pacientes com leucemia mielóide crônica |
dc.title.alternative.eng.fl_str_mv |
Evaluation of tyrosine kinase inhibitors for use in patients with chronic myeloid leukemia |
title |
Avaliação do uso de inibidores de tirosina quinase em pacientes com leucemia mielóide crônica |
spellingShingle |
Avaliação do uso de inibidores de tirosina quinase em pacientes com leucemia mielóide crônica Goulart, Valéria Pereira Leucemia mieloide crônica Inibidores tirosina quinase Resposta Efetividade Chronic myeloid leukemia Tyrosine kinase inhibitors Response Effectiviness CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Avaliação do uso de inibidores de tirosina quinase em pacientes com leucemia mielóide crônica |
title_full |
Avaliação do uso de inibidores de tirosina quinase em pacientes com leucemia mielóide crônica |
title_fullStr |
Avaliação do uso de inibidores de tirosina quinase em pacientes com leucemia mielóide crônica |
title_full_unstemmed |
Avaliação do uso de inibidores de tirosina quinase em pacientes com leucemia mielóide crônica |
title_sort |
Avaliação do uso de inibidores de tirosina quinase em pacientes com leucemia mielóide crônica |
author |
Goulart, Valéria Pereira |
author_facet |
Goulart, Valéria Pereira |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Silva, José Edson Paz da |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/1177504021154172 |
dc.contributor.advisor-co1.fl_str_mv |
Cóser, Virgínia Maria |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/4601008307298787 |
dc.contributor.referee1.fl_str_mv |
Oliveira, Daniele Carvalho de |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/4817827751698191 |
dc.contributor.referee2.fl_str_mv |
Duarte, Marta Maria Medeiros Frescura |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/6277584896102052 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/7757176869080085 |
dc.contributor.author.fl_str_mv |
Goulart, Valéria Pereira |
contributor_str_mv |
Silva, José Edson Paz da Cóser, Virgínia Maria Oliveira, Daniele Carvalho de Duarte, Marta Maria Medeiros Frescura |
dc.subject.por.fl_str_mv |
Leucemia mieloide crônica Inibidores tirosina quinase Resposta Efetividade |
topic |
Leucemia mieloide crônica Inibidores tirosina quinase Resposta Efetividade Chronic myeloid leukemia Tyrosine kinase inhibitors Response Effectiviness CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Chronic myeloid leukemia Tyrosine kinase inhibitors Response Effectiviness |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Chronic myeloid leukemia (CML) results from the clonal proliferation of a hematopoietic stem cell representing approximately 15-20% of all cases of leukemia. It is characterized by the presence of the Philadelphia chromosome (Ph), which is the result of the reciprocal translocation between chromosomes 9 and 22. The molecular consequence of translocation is the formation of a hybrid gene, BCR-ABL, encoding a chimeric protein with an intense and dysregulated tyrosine kinase activity, thereby, providing the phenotype of the disease. Over the years, there have been several therapeutic landmarks in the treatment of CML, from busulfan and hydroxyurea until the advent of allogeneic Hematopoietic Stem Cell Transplantation (HSCT) and alpha-interferon. Imatinib mesylate, the first selective tyrosine kinase inhibitor, has been approved by regulatory authorities in 2001 and since that revolutionized the treatment of CML, producing the best therapeutic effects already achieved, except for the HSCT. The excellent clinical results with this drug turned it into the treatment of choice for newly diagnosed patients. Tyrosine kinase second generation inhibitors, such as nilotinib and dasatinib, have been developed having a higher power in order to decrease the chance of disease resistance and expand treatment further options. Presently these drugs are more specific and effective because they are able to trigger a response to the hematological, cytogenetic and molecular level, allowing the patient to have an overall survival practically equal to the general population as well as a quality of life. This cohort study does a retrospective by analyzing medical records of patients with CML treated with tyrosine kinase inhibitors at the University Hospital of Santa Maria (UHSM), attended by the Unified Health System (UHS), describes the epidemiology of this disease in the institution, its evolution in terms of hematologic responses, cytogenetic and molecular, overall survival (OS), progression-free survival (PFS), event-free survival (EFS) and more frequent adverse effects. 98 patients were included, 88.8% in chronic phase, with a mean age of 47.36 years and 58.2% of them were men. About the adverse effects, the most frequent ones were the cramp, myalgia rash and 20%, 15%, 14% respectively. Twelve patients had additional cytogenetic changes to the Ph chromosome, and 50% of these changes were related to worsening of the disease. The HCR was achieved by 91.88%, 84% and 58.33% of patients using imatinib, Dasatinib and Nilotinib respectively. Molecular response was obtained by 78.55% of patients treated with Imatinib, 72% with Dasatinib and 58.7% with Nilotinib. The probability of OS was 95% for 60 months, while PFS and EFS, in the same period, was 85.4% and 69.4% respectively. Patients treated with tyrosine kinase inhibitors in HUSM showed a high frequency of hematological and molecular responses, PFS and OS similar to those described in the world's literature, justifying the investment made by SUS in the purchase of this product. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016-08-26 |
dc.date.accessioned.fl_str_mv |
2019-08-29T13:32:31Z |
dc.date.available.fl_str_mv |
2019-08-29T13:32:31Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/18069 |
url |
http://repositorio.ufsm.br/handle/1/18069 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
201000000000 |
dc.relation.confidence.fl_str_mv |
600 |
dc.relation.authority.fl_str_mv |
f31cbb2c-a6b3-42b5-99ec-4f7ceeff6149 239f6aa8-673e-439f-a089-2f1ad92d0748 45fd1a17-92a3-40f6-a132-468542b69d10 4ca8dea0-e54c-432c-9fde-f3f307c4dbb7 558a0333-9455-4f48-b3ef-9e36524ab97f |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Farmacêuticas |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Análises Clínicas e Toxicológicas |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações do UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Biblioteca Digital de Teses e Dissertações do UFSM |
collection |
Biblioteca Digital de Teses e Dissertações do UFSM |
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MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1801485112148230144 |