Factores asociados a supervivencia en pacientes con leucemia linfoblástica aguda

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dc.contributor.advisorSossa Melo, Claudia Lucía
dc.contributor.advisorMorales Chacón, Katherinee
dc.contributor.advisorOchoa Vera, Miguel Enrique
dc.contributor.advisorLuna González , María Lucrecia
dc.contributor.apolounabSossa Melo, Claudia Lucía [claudia-lucia-sossa-melo]spa
dc.contributor.apolounabLuna González , María Lucrecia Lucrecia [maría-lucrecia-luna-gonzález]spa
dc.contributor.apolounabOchoa Vera, Miguel Enrique [miguel-enrique-ochoa-vera]spa
dc.contributor.apolounabLuna González , María Lucrecia [maría-lucrecia-luna-gonzález]spa
dc.contributor.authorSossa Pinzón, Luis Alfredo
dc.contributor.cvlacOchoa Vera, Miguel Enrique [0000898465]spa
dc.contributor.cvlacLuna González, Maria Lucrecia [0001347422]spa
dc.contributor.cvlacSossa Melo, Claudia Lucía [0001425704]spa
dc.contributor.cvlacMorales Chacón, Katherinee [0001618150]spa
dc.contributor.orcidSossa Pinzón, Luis Alfredo [0009-0007-6521-9280]spa
dc.contributor.orcidMorales Chacón, Katherinee [0000-0001-6394-6811]spa
dc.contributor.orcidLuna González , María Lucrecia [0000-0003-2846-6868]spa
dc.contributor.orcidOchoa Vera, Miguel Enrique [0000-0002-4552-3388]spa
dc.contributor.orcidSossa Melo, Claudia Lucía [0000-0001-9876-222X]spa
dc.contributor.researchgroupGrupo de Investigaciones Clínicasspa
dc.coverage.campusUNAB Campus Bucaramangaspa
dc.coverage.spatialFloridablanca (Santander, Colombia)spa
dc.coverage.temporal2024 - 2025spa
dc.date.accessioned2025-06-26T15:46:52Z
dc.date.available2025-06-26T15:46:52Z
dc.date.issued2025-06-16
dc.degree.nameEspecialista en Medicina Internaspa
dc.description.abstractEstudio observacional de cohorte retrospectiva que evaluó los factores clínicos, biológicos y terapéuticos asociados con la supervivencia global (SG) y la supervivencia libre de enfermedad (SLE) en pacientes adultos con leucemia linfoblástica aguda (LLA) tratados entre 2013 y 2022 en la Fundación oftalmológica de Santander Foscal y Fundación Fosunab. Se incluyeron pacientes mayores de 18 años con diagnóstico confirmado de LLA, excluyéndose aquellos con antecedentes de neoplasias sólidas, VIH/sida o trasplante de órgano sólido. El análisis consideró variables sociodemográficas, comorbilidades, estado funcional, hallazgos de laboratorio, características del tratamiento (incluido blinatumomab) y respuesta terapéutica. La información fue obtenida de una base de datos anonimizada estructurada previamente. Se calcularon curvas de Kaplan-Meier y modelos de regresión de Cox para estimar razones de riesgo (HR) y sus respectivos intervalos de confianza (IC95%). La mediana de SG fue de 18,3 meses y de SLE de 14,2 meses. Se identificaron como factores asociados a menor SG y SLE la presencia de diabetes mellitus, obesidad, arritmias, estado funcional deteriorado (ECOG 4), recaídas extramedulares y posterior a la consolidación. Por el contrario, se asociaron a mayor SG y SLE la escolaridad secundaria, fondo de ojo sin hallazgos, terapia de mantenimiento, uso de blinatumomab con remisión morfológica y enfermedad mínima residual negativa, así como el trasplante hematopoyético. El estudio fue aprobado por el Comité de Ética institucional y clasificado como de riesgo mínimo según la Resolución 8430 de 1993.spa
dc.description.abstractenglishThis was a retrospective cohort observational study aimed at evaluating clinical, biological, and therapeutic factors associated with overall survival (OS) and disease-free survival (DFS) in adult patients with acute lymphoblastic leukemia (ALL) treated between 2013 and 2022 at Fundación Oftalmológica de Santander Foscal and Fundación Fosunab. Patients aged over 18 years with a confirmed diagnosis of ALL were included, excluding those with a history of solid neoplasms, HIV/AIDS, or solid organ transplantation. The analysis considered sociodemographic characteristics, comorbidities, functional status, laboratory findings, treatment-related variables (including blinatumomab), and therapeutic response. Data were obtained from a previously structured and anonymized database. Kaplan–Meier survival curves and Cox proportional hazards models were used to estimate hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI). The median OS was 18.3 months, and the median DFS was 14.2 months. Factors associated with lower OS and DFS included diabetes mellitus, obesity, arrhythmias, poor functional status (ECOG 4), extramedullary relapse, and post-consolidation relapse. In contrast, secondary education level, absence of fundoscopic abnormalities, maintenance therapy, use of blinatumomab achieving morphological remission with negative minimal residual disease, and hematopoietic stem cell transplantation were associated with improved OS and DFS. The study was approved by the Institutional Ethics Committee and classified as minimal risk in accordance with Resolution 8430 of 1993.spa
dc.description.degreelevelEspecializaciónspa
dc.description.learningmodalityModalidad Presencialspa
dc.description.tableofcontentsPlanteamiento del Problema ............................................................................................ 7 Justificación ................................................................................................................... 10 Marco teórico ................................................................................................................. 12 Definición de la Leucemia Linfoblástica Aguda ..................................................... 12 Subtipos de LLA ................................................................................................... 13 Características Clínicas ........................................................................................ 14 Laboratorios ......................................................................................................... 15 Análisis Morfológico y Citoquímico ....................................................................... 16 Características Inmunológicas .............................................................................. 17 Clasificación Genética .......................................................................................... 18 Síndromes Genéticos .................................................................................................... 19 Leucemia Familiar ................................................................................................ 19 Factores Ambientales ........................................................................................... 20 Alteraciones Genéticas Adquiridas ....................................................................... 20 Factores de Riesgo .............................................................................................. 21 Etapas de la Enfermedad ..................................................................................... 22 Principales Avances en el Diagnóstico ................................................................. 22 Tratamiento en el contexto actual ......................................................................... 23 Curso, pronóstico y reacciones adversas en el tratamiento .................................. 24 Estado del Arte .............................................................................................................. 26 Pregunta de Investigación ............................................................................................. 35 Hipótesis ........................................................................................................................ 35 Objetivos ....................................................................................................................... 35 Objetivo General .................................................................................................. 35 Objetivos específicos ............................................................................................ 35 Metodología ................................................................................................................... 36 Tipo de estudio ..................................................................................................... 36 Población ............................................................................................................. 36 Criterios de inclusión ............................................................................................ 36 Criterios de exclusión ........................................................................................... 36 Cálculo de tamaño de muestra ............................................................................. 36 Recolección de la información .............................................................................. 37 Definición de Supervivencia ................................................................................. 38 Plan de Análisis .................................................................................................... 38 FACTORES ASOCIADOS A SUPERVIVENCIA EN PACIENTES CON LLA 3 Versión 1. Mayo 19 de 2025 Consideraciones Éticas ........................................................................................ 39 Resultados..................................................................................................................... 40 Factores biológicos, clínicos y terapéuticos de los pacientes con LLA del estudio ......... 40 Características de los pacientes con uso de blinatumomab en terapia de rescate ......... 56 Características de los pacientes con TPH ..................................................................... 59 Resultados a largo plazo ............................................................................................... 61 Sobrevida global (SG) .......................................................................................... 64 Sobrevida libre de enfermedad (SLE) ................................................................... 93 SG y SLE por AYAS versus No AYAS ......................................................................... 117 Discusión ..................................................................................................................... 120 Factores Asociados a Mejor SG ......................................................................... 122 Factores Asociado a menor SG .......................................................................... 124 Factores Asociados a Mejor SLE ........................................................................ 125 Factores Asociado a Menor SLE ........................................................................ 126 AYAS y NO AYAS .............................................................................................. 127 Características de la población tratada con Blinatumomab ................................. 128 Limitaciones y Fortalezas ............................................................................................ 129 Conclusión ................................................................................................................... 131 Referencias bibliográficas ............................................................................................ 133 Anexos ........................................................................................................................ 144spa
dc.format.mimetypeapplication/pdfspa
dc.identifier.instnameinstname:Universidad Autónoma de Bucaramanga - UNABspa
dc.identifier.reponamereponame:Repositorio Institucional UNABspa
dc.identifier.repourlrepourl:https://repository.unab.edu.cospa
dc.identifier.urihttp://hdl.handle.net/20.500.12749/30089
dc.language.isospaspa
dc.publisher.facultyFacultad Ciencias de la Saludspa
dc.publisher.grantorUniversidad Autónoma de Bucaramanga UNABspa
dc.publisher.programEspecialización en Medicina Internaspa
dc.publisher.programidEMIN-1050
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dc.relation.referencesChessells JM. Central nervous system directed therapy in acute lymphoblastic leukaemia. Baillieres Clin Haematol. 1994 Jun;7(2):349–63.spa
dc.relation.referencesTurtle CJ, Hanafi LA, Berger C, Gooley TA, Cherian S, Hudecek M, et al. CD19 CAR–T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. Journal of Clinical Investigation. 2016 Apr 25;126(6):2123–38.spa
dc.relation.referencesRichard-Carpentier G, Jabbour E, Short NJ, Rausch CR, Savoy JM, Bose P, et al. Clinical Experience With. Venetoclax Combined With Chemotherapy for Relapsed or Refractory T- Cell Acute Lymphoblastic Leukemia. Clin Lymphoma Myeloma Leuk. 2020 Apr;20(4):212 8.spa
dc.relation.referencesStock W, Johnson JL, Stone RM, Kolitz JE, Powell BL, Wetzler M, et al. Dose intensification of daunorubicin and cytarabine during treatment of adult acute lymphoblastic leukemia. Cancer. 2013 Jan 28;119(1):90–8.spa
dc.relation.referencesChiu EK, Chan LC, Liang R, Lie A, Kwong YL, Todd D, et al. Poor outcome of intensive chemotherapy for adult acute lymphoblastic leukemia: a possible dose effect. Leukemia. 1994 Sep;8(9):1469–73.spa
dc.relation.referencesYu J, Ge X, Luo Y, Shi J, Tan Y, Lai X, et al. Incidence, risk factors and outcome of extramedullary relapse after allogeneic hematopoietic stem cell transplantation in patients with adult acute lymphoblastic leukemia. Ann Hematol. 2020 Nov 5;99(11):2639–48.spa
dc.relation.referencesSchneidawind C, Hagmaier V, Faul C, Kanz L, Bethge W, Schneidawind D. Second allogeneic hematopoietic cell transplantation enables long-term disease-free survival in relapsed acute leukemia. Ann Hematol. 2018 Dec 31;97(12):2491–500.spa
dc.relation.referencesCharafeddine KM, Hatoum HA, Otrock ZK, Mahfouz RA, Salem ZM, Shamseddine AI, et al. Long-term outcome of adult acute lymphoblastic leukemia in Lebanon. Hematol Oncol Stem Cell Ther. 2009 Apr;2(2):333–9.spa
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dc.relation.referencesLe Q, Thomas X, Ecochard R, Iwaz J, Lheéritier V, Michallet M, et al. Proportion of long term event‐free survivors and lifetime of adult patients not cured after a standard acute lymphoblastic leukemia therapeutic program. Cancer. 2007 May 15;109(10):2058–67.spa
dc.relation.referencesBrown PA, Ji L, Xu X, Devidas M, Hogan LE, Borowitz MJ, et al. Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia. JAMA. 2021 Mar 2;325(9):833.spa
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dc.relation.uriapolohttps://apolo.unab.edu.co/en/persons/claudia-lucia-sossa-melospa
dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.creativecommonsAtribución-NoComercial-SinDerivadas 2.5 Colombia*
dc.rights.localAbierto (Texto Completo)spa
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/2.5/co/*
dc.subject.keywordsInternal medicinespa
dc.subject.keywordsMedicinespa
dc.subject.keywordsMedical sciencesspa
dc.subject.keywordsHealth sciencesspa
dc.subject.keywordsAcute lymphoblastic leukemiaspa
dc.subject.keywordsOverall survivalspa
dc.subject.keywordsDisease-free survivalspa
dc.subject.keywordsBlinatumomabspa
dc.subject.keywordsPrognostic factorsspa
dc.subject.keywordsHematopoietic stem cell transplantationspa
dc.subject.keywordsMeasurable residual diseasespa
dc.subject.keywordsBone marrow (Diseases)spa
dc.subject.keywordsImmunotherapyspa
dc.subject.keywordsImmunology clinicspa
dc.subject.keywordsVital Statisticsspa
dc.subject.keywordsDemographyspa
dc.subject.lembMedicina internaspa
dc.subject.lembMedicinaspa
dc.subject.lembCiencias médicasspa
dc.subject.lembMédula ósea (Enfermedades)spa
dc.subject.lembInmunoterapiaspa
dc.subject.lembInmunología clínicaspa
dc.subject.lembEstadística vitalspa
dc.subject.lembDemografíaspa
dc.subject.proposalCiencias de la saludspa
dc.subject.proposalLeucemia linfoblástica agudaspa
dc.subject.proposalSobrevida globalspa
dc.subject.proposalSobrevida libre de enfermedadspa
dc.subject.proposalTrasplante hematopoyéticospa
dc.subject.proposalFactores pronósticosspa
dc.subject.proposalEnfermedad residual mediblespa
dc.titleFactores asociados a supervivencia en pacientes con leucemia linfoblástica agudaspa
dc.title.translatedPrognostic Factors for Survival in Patients with Acute Lymphoblastic Leukemiaspa
dc.type.coarhttp://purl.org/coar/resource_type/c_bdcc
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aaspa
dc.type.driverinfo:eu-repo/semantics/masterThesis
dc.type.hasversioninfo:eu-repo/semantics/acceptedVersion
dc.type.localTesisspa
dc.type.redcolhttp://purl.org/redcol/resource_type/TM

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Especialización en Medicina Interna
Grupo de Investigaciones Clínicas