Avaliação clínico-epidemiológica e molecular de pacientes com leucemia linfocítica crônica atendidos no Hospital Universitário Walter Cantídio

Detalhes bibliográficos
Autor(a) principal: Lopes, Germison Silva
Data de Publicação: 2019
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/53851
Resumo: Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disease characterized by the accumulation of clonal B lymphocytes with coexpression of CD19 and CD5, in addition to CD 23, weak CD 20 and negativity for FMC7. According to the World Health Organization (WHO), more than 5,000 / mm³ B lymphocytes with persistent suggestive phenotype are required for at least 3 months. It is the most prevalent leukemia in adults in the West. It has an indolent behavior with lower survival than the general population, but still prolonged. It is predominantly male and affects older individuals, especially over 65 years. Pathophysiology has two main points: loss of apoptosis capacity and proliferative stimulation. This was a cross-sectional study of 147 patients diagnosed with chronic lymphocytic leukemia followed during the period of 02/03/2017 and 30/04/2019 at the outpatient clinic of chronic lymphoproliferative diseases at Walter Cantídio University Hopsital. Sociodemographic and molecular variables and their relationship with time to first treatment and overall survival were analyzed. For statistical analysis, GraphPad Prisma 7 software was used. The median age of diagnosis was 70 years, with a slight predominance in males, with a ratio of 1.13: 1. The origin of 66% of the patients came from the metropolitan region of Fortaleza. Diagnosis was made by peripheral blood flow cytometry in more than 90% of patients. Direct antiglobulin test was positive in 11%. 58% were staged as BINET A, 13% as B and 29% as C. For modified RAI staging, 34% were low risk, 36% intermediate risk and 30% high risk. IGHV status was mutated in 49% and not mutated in 34% of patients. TP53 mutation was present in 5 patients. The median time to first treatment (TPPT) was 3.2 years. Factors related to higher TPPT were: age <60 years (p = 0.491), female gender (p = 0.0052), hemoglobin ≥10g / dL and lymphometry <50,000 / mm³ at diagnosis (p = 0.0001), platelet analysis at diagnosis ≥100,000 / mm³ (p = 0.0054), low risk modified BINET A and RAI staging (p = 0.0001) and mutated IGHV (p = 0.0293). The median overall survival (SG) of CLL patients was 12 years. Factors related to longer survival were: female gender (p = 0.0152), hemoglobin at diagnosis ≥10g / dL (p = 0.0005), lymphometry <50,000 / mm³ at diagnosis (p = 0.0174), BINET staging A (p = 0.0105), modified low-risk RAI (p = 0.0023) and no previous treatment (p = 0.0023). Unlike in other countries, a slightly higher prevalence was observed in males, but when considering individuals over 65 years, it is more prevalent in females. Older patients had no worse prognostic factors when stratified by socio-demographic and molecular variables. Mutated IGHV status was related to higher TPPT, but not to SG. The presence of TP53 mutation was not related to lower TPPT or SG. Knowing the clinical and epidemiological data of the patients with CLL and the risk factors for shorter time to treatment and shorter overall survival contributes to better management of this condition and assists in health service programming.
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spelling Avaliação clínico-epidemiológica e molecular de pacientes com leucemia linfocítica crônica atendidos no Hospital Universitário Walter CantídioLeucemia Linfocítica Crônica de Células BSobrevidaChronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disease characterized by the accumulation of clonal B lymphocytes with coexpression of CD19 and CD5, in addition to CD 23, weak CD 20 and negativity for FMC7. According to the World Health Organization (WHO), more than 5,000 / mm³ B lymphocytes with persistent suggestive phenotype are required for at least 3 months. It is the most prevalent leukemia in adults in the West. It has an indolent behavior with lower survival than the general population, but still prolonged. It is predominantly male and affects older individuals, especially over 65 years. Pathophysiology has two main points: loss of apoptosis capacity and proliferative stimulation. This was a cross-sectional study of 147 patients diagnosed with chronic lymphocytic leukemia followed during the period of 02/03/2017 and 30/04/2019 at the outpatient clinic of chronic lymphoproliferative diseases at Walter Cantídio University Hopsital. Sociodemographic and molecular variables and their relationship with time to first treatment and overall survival were analyzed. For statistical analysis, GraphPad Prisma 7 software was used. The median age of diagnosis was 70 years, with a slight predominance in males, with a ratio of 1.13: 1. The origin of 66% of the patients came from the metropolitan region of Fortaleza. Diagnosis was made by peripheral blood flow cytometry in more than 90% of patients. Direct antiglobulin test was positive in 11%. 58% were staged as BINET A, 13% as B and 29% as C. For modified RAI staging, 34% were low risk, 36% intermediate risk and 30% high risk. IGHV status was mutated in 49% and not mutated in 34% of patients. TP53 mutation was present in 5 patients. The median time to first treatment (TPPT) was 3.2 years. Factors related to higher TPPT were: age <60 years (p = 0.491), female gender (p = 0.0052), hemoglobin ≥10g / dL and lymphometry <50,000 / mm³ at diagnosis (p = 0.0001), platelet analysis at diagnosis ≥100,000 / mm³ (p = 0.0054), low risk modified BINET A and RAI staging (p = 0.0001) and mutated IGHV (p = 0.0293). The median overall survival (SG) of CLL patients was 12 years. Factors related to longer survival were: female gender (p = 0.0152), hemoglobin at diagnosis ≥10g / dL (p = 0.0005), lymphometry <50,000 / mm³ at diagnosis (p = 0.0174), BINET staging A (p = 0.0105), modified low-risk RAI (p = 0.0023) and no previous treatment (p = 0.0023). Unlike in other countries, a slightly higher prevalence was observed in males, but when considering individuals over 65 years, it is more prevalent in females. Older patients had no worse prognostic factors when stratified by socio-demographic and molecular variables. Mutated IGHV status was related to higher TPPT, but not to SG. The presence of TP53 mutation was not related to lower TPPT or SG. Knowing the clinical and epidemiological data of the patients with CLL and the risk factors for shorter time to treatment and shorter overall survival contributes to better management of this condition and assists in health service programming.A leucemia linfocítica crônica (LLC) é uma doença linfoproliferativa crônica caracterizada pelo acúmulo de linfócitos B clonais com coexpressão de CD19 e CD 5, além de CD 23, CD 20 fraco e negatividade para FMC7. De acordo com a Organização Mundial da Saúde (OMS), são necessários mais de 5.000/mm³ linfócitos B com fenótipo sugestivo persistente por pelo menos 3 meses. É a leucemia mais prevalente em adultos no ocidente. Tem um comportamento indolente com sobrevida menor do que a da população geral, porém ainda prolongada. Tem predominância no sexo masculino e acomete indivíduos mais idosos, especialmente acima de 65 anos. A fisiopatologia tem dois pontos principais: perda da capacidade de apoptose e estímulo proliferativo. Trata-se de um estudo de transversal de avaliação de 147 pacientes com diagnóstico de leucemia linfocítica crônica acompanhados durante o período de 02/03/2017 e 30/04/2019 no ambulatório de doenças linfoproliferativas crônicas do Hopsital Universitário Walter Cantídio. Foram analisadas variáveis sócio-demográficas e moleculares e sua relação com o tempo para primeiro tratamento e sobrevida global. Foram utilizados os testes exato de Fisher, qui-quadrado de Pearson (χ2), t de Student, ANOVA, U de Mann-Whitney e Kruskal-Wallis . A idade mediana de diagnóstico foi de 70 anos, com discreto predomínio no sexo masculino, com relação de 1,13:1. A procedência de 66% dos pacientes foi da região metropolitana de Fortaleza. O diagnóstico foi feito por citometria de fluxo do sangue periférico em mais de 90% dos pacientes. O teste de antiglobulina direto foi positivo em 11%. 58% foram estadiados como BINET A, 13% como B e 29% como C. Já para o estadiamento de RAI modificado, 34% eram de baixo risco, 36% de risco intermediário e 30% de alto risco. O status IGHV foi mutado em 49% e não mutado em 34% dos pacientes. A mutação do TP53 estava presente em 5 pacientes. A mediana de tempo para primeiro tratamento (TPPT) foi de 3,2 anos. Os fatores relacionados com maior TPPT foram: idade < 60 anos (p=0,491), sexo feminino (p =0,0052), hemoglobina ≥10g/dL e linfometria <50.000/mm³ ao diagnóstico (p = 0,0001), plaquetometria ao diagnóstico ≥100.000/mm³ (p=0,0054), estadiamento BINET A e RAI modificado de baixo risco (p=0,0001) e IGHV mutado (p=0,0293). A mediana de sobrevida global (SG) dos pacientes com LLC foi de12anos. Os fatores relacionados com maior sobrevida foram: sexo feminino (p =0,0152), hemoglobina ao diagnóstico ≥10g/dL (p=0,0005), linfometria <50.000/mm³ ao diagnóstico (p = 0,0174), estadiamento BINET A (p=0,0105), RAI modificado de baixo risco (p=0,0023) e não ter feito nenhum tratamento prévio (p=0,0023). Diferente do observado em outros países, foi observado uma discreta maior prevalência no sexo masculino, porém, quando considerados os indivíduos com mais de 65 anos, é mais prevalente no sexo feminino. Os pacientes mais idosos não apresentavam fatores de pior prognóstico quando estratificados por variáveis sócio-demograficas e moleculares. O status IGHV mutado foi relacionado com maior TPPT, mas não com a SG. A presença da mutação do TP53 não foi relacionada a menor TPPT ou SG. O conhecimento dos dados clínico epidemiológicos dos pacientes estudados e dos fatores de risco para menor tempo até tratamento e menor sobrevida global contribui para o melhor manejo dessa condição e auxilia na programação do serviço de sáude.Montenegro, Raquel CarvalhoNunes, Caroline de Fátima Aquino MoreiraLopes, Germison Silva2020-09-04T18:03:05Z2020-09-04T18:03:05Z2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfLOPES, Germison Silva. Avaliação clínico-epidemiológica e molecular de pacientes com leucemia linfocítica crônica atendidos no Hospital Universitário Walter Cantídio. 2019. 89 f. Dissertação (Mestrado Profissional em Farmacologia Clínica) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2019.http://www.repositorio.ufc.br/handle/riufc/53851porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2020-09-04T18:03:05Zoai:repositorio.ufc.br:riufc/53851Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:28:43.928328Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Avaliação clínico-epidemiológica e molecular de pacientes com leucemia linfocítica crônica atendidos no Hospital Universitário Walter Cantídio
title Avaliação clínico-epidemiológica e molecular de pacientes com leucemia linfocítica crônica atendidos no Hospital Universitário Walter Cantídio
spellingShingle Avaliação clínico-epidemiológica e molecular de pacientes com leucemia linfocítica crônica atendidos no Hospital Universitário Walter Cantídio
Lopes, Germison Silva
Leucemia Linfocítica Crônica de Células B
Sobrevida
title_short Avaliação clínico-epidemiológica e molecular de pacientes com leucemia linfocítica crônica atendidos no Hospital Universitário Walter Cantídio
title_full Avaliação clínico-epidemiológica e molecular de pacientes com leucemia linfocítica crônica atendidos no Hospital Universitário Walter Cantídio
title_fullStr Avaliação clínico-epidemiológica e molecular de pacientes com leucemia linfocítica crônica atendidos no Hospital Universitário Walter Cantídio
title_full_unstemmed Avaliação clínico-epidemiológica e molecular de pacientes com leucemia linfocítica crônica atendidos no Hospital Universitário Walter Cantídio
title_sort Avaliação clínico-epidemiológica e molecular de pacientes com leucemia linfocítica crônica atendidos no Hospital Universitário Walter Cantídio
author Lopes, Germison Silva
author_facet Lopes, Germison Silva
author_role author
dc.contributor.none.fl_str_mv Montenegro, Raquel Carvalho
Nunes, Caroline de Fátima Aquino Moreira
dc.contributor.author.fl_str_mv Lopes, Germison Silva
dc.subject.por.fl_str_mv Leucemia Linfocítica Crônica de Células B
Sobrevida
topic Leucemia Linfocítica Crônica de Células B
Sobrevida
description Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disease characterized by the accumulation of clonal B lymphocytes with coexpression of CD19 and CD5, in addition to CD 23, weak CD 20 and negativity for FMC7. According to the World Health Organization (WHO), more than 5,000 / mm³ B lymphocytes with persistent suggestive phenotype are required for at least 3 months. It is the most prevalent leukemia in adults in the West. It has an indolent behavior with lower survival than the general population, but still prolonged. It is predominantly male and affects older individuals, especially over 65 years. Pathophysiology has two main points: loss of apoptosis capacity and proliferative stimulation. This was a cross-sectional study of 147 patients diagnosed with chronic lymphocytic leukemia followed during the period of 02/03/2017 and 30/04/2019 at the outpatient clinic of chronic lymphoproliferative diseases at Walter Cantídio University Hopsital. Sociodemographic and molecular variables and their relationship with time to first treatment and overall survival were analyzed. For statistical analysis, GraphPad Prisma 7 software was used. The median age of diagnosis was 70 years, with a slight predominance in males, with a ratio of 1.13: 1. The origin of 66% of the patients came from the metropolitan region of Fortaleza. Diagnosis was made by peripheral blood flow cytometry in more than 90% of patients. Direct antiglobulin test was positive in 11%. 58% were staged as BINET A, 13% as B and 29% as C. For modified RAI staging, 34% were low risk, 36% intermediate risk and 30% high risk. IGHV status was mutated in 49% and not mutated in 34% of patients. TP53 mutation was present in 5 patients. The median time to first treatment (TPPT) was 3.2 years. Factors related to higher TPPT were: age <60 years (p = 0.491), female gender (p = 0.0052), hemoglobin ≥10g / dL and lymphometry <50,000 / mm³ at diagnosis (p = 0.0001), platelet analysis at diagnosis ≥100,000 / mm³ (p = 0.0054), low risk modified BINET A and RAI staging (p = 0.0001) and mutated IGHV (p = 0.0293). The median overall survival (SG) of CLL patients was 12 years. Factors related to longer survival were: female gender (p = 0.0152), hemoglobin at diagnosis ≥10g / dL (p = 0.0005), lymphometry <50,000 / mm³ at diagnosis (p = 0.0174), BINET staging A (p = 0.0105), modified low-risk RAI (p = 0.0023) and no previous treatment (p = 0.0023). Unlike in other countries, a slightly higher prevalence was observed in males, but when considering individuals over 65 years, it is more prevalent in females. Older patients had no worse prognostic factors when stratified by socio-demographic and molecular variables. Mutated IGHV status was related to higher TPPT, but not to SG. The presence of TP53 mutation was not related to lower TPPT or SG. Knowing the clinical and epidemiological data of the patients with CLL and the risk factors for shorter time to treatment and shorter overall survival contributes to better management of this condition and assists in health service programming.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020-09-04T18:03:05Z
2020-09-04T18:03:05Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
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dc.identifier.uri.fl_str_mv LOPES, Germison Silva. Avaliação clínico-epidemiológica e molecular de pacientes com leucemia linfocítica crônica atendidos no Hospital Universitário Walter Cantídio. 2019. 89 f. Dissertação (Mestrado Profissional em Farmacologia Clínica) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2019.
http://www.repositorio.ufc.br/handle/riufc/53851
identifier_str_mv LOPES, Germison Silva. Avaliação clínico-epidemiológica e molecular de pacientes com leucemia linfocítica crônica atendidos no Hospital Universitário Walter Cantídio. 2019. 89 f. Dissertação (Mestrado Profissional em Farmacologia Clínica) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2019.
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reponame_str Repositório Institucional da Universidade Federal do Ceará (UFC)
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