Factores asociados a supervivencia en pacientes con leucemia linfoblástica aguda

Estudio 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 of...

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Autores:: Sossa Pinzón, Luis Alfredo

Tipo de recurso:

Fecha de publicación:: 2025

Institución:: Universidad Autónoma de Bucaramanga - UNAB

Repositorio:: Repositorio UNAB

Idioma:: spa

id	UNAB2_cbaea3dd31c543c7e22e53e125510d06
oai_identifier_str	oai:repository.unab.edu.co:20.500.12749/30089
network_acronym_str	UNAB2
network_name_str	Repositorio UNAB
repository_id_str
dc.title.spa.fl_str_mv	Factores asociados a supervivencia en pacientes con leucemia linfoblástica aguda
dc.title.translated.spa.fl_str_mv	Prognostic Factors for Survival in Patients with Acute Lymphoblastic Leukemia
title	Factores asociados a supervivencia en pacientes con leucemia linfoblástica aguda
spellingShingle	Factores asociados a supervivencia en pacientes con leucemia linfoblástica aguda Internal medicine Medicine Medical sciences Health sciences Acute lymphoblastic leukemia Overall survival Disease-free survival Blinatumomab Prognostic factors Hematopoietic stem cell transplantation Measurable residual disease Bone marrow (Diseases) Immunotherapy Immunology clinic Vital Statistics Demography Medicina interna Medicina Ciencias médicas Médula ósea (Enfermedades) Inmunoterapia Inmunología clínica Estadística vital Demografía Ciencias de la salud Leucemia linfoblástica aguda Sobrevida global Sobrevida libre de enfermedad Trasplante hematopoyético Factores pronósticos Enfermedad residual medible
title_short	Factores asociados a supervivencia en pacientes con leucemia linfoblástica aguda
title_full	Factores asociados a supervivencia en pacientes con leucemia linfoblástica aguda
title_fullStr	Factores asociados a supervivencia en pacientes con leucemia linfoblástica aguda
title_full_unstemmed	Factores asociados a supervivencia en pacientes con leucemia linfoblástica aguda
title_sort	Factores asociados a supervivencia en pacientes con leucemia linfoblástica aguda
dc.creator.fl_str_mv	Sossa Pinzón, Luis Alfredo
dc.contributor.advisor.none.fl_str_mv	Sossa Melo, Claudia Lucía Morales Chacón, Katherinee Ochoa Vera, Miguel Enrique Luna González , María Lucrecia
dc.contributor.author.none.fl_str_mv	Sossa Pinzón, Luis Alfredo
dc.contributor.cvlac.spa.fl_str_mv	Ochoa Vera, Miguel Enrique [0000898465] Luna González, Maria Lucrecia [0001347422] Sossa Melo, Claudia Lucía [0001425704] Morales Chacón, Katherinee [0001618150]
dc.contributor.orcid.spa.fl_str_mv	Sossa Pinzón, Luis Alfredo [0009-0007-6521-9280] Morales Chacón, Katherinee [0000-0001-6394-6811] Luna González , María Lucrecia [0000-0003-2846-6868] Ochoa Vera, Miguel Enrique [0000-0002-4552-3388] Sossa Melo, Claudia Lucía [0000-0001-9876-222X]
dc.contributor.researchgroup.spa.fl_str_mv	Grupo de Investigaciones Clínicas
dc.contributor.apolounab.spa.fl_str_mv	Sossa Melo, Claudia Lucía [claudia-lucia-sossa-melo] Luna González , María Lucrecia Lucrecia [maría-lucrecia-luna-gonzález] Ochoa Vera, Miguel Enrique [miguel-enrique-ochoa-vera] Luna González , María Lucrecia [maría-lucrecia-luna-gonzález]
dc.subject.keywords.spa.fl_str_mv	Internal medicine Medicine Medical sciences Health sciences Acute lymphoblastic leukemia Overall survival Disease-free survival Blinatumomab Prognostic factors Hematopoietic stem cell transplantation Measurable residual disease Bone marrow (Diseases) Immunotherapy Immunology clinic Vital Statistics Demography
topic	Internal medicine Medicine Medical sciences Health sciences Acute lymphoblastic leukemia Overall survival Disease-free survival Blinatumomab Prognostic factors Hematopoietic stem cell transplantation Measurable residual disease Bone marrow (Diseases) Immunotherapy Immunology clinic Vital Statistics Demography Medicina interna Medicina Ciencias médicas Médula ósea (Enfermedades) Inmunoterapia Inmunología clínica Estadística vital Demografía Ciencias de la salud Leucemia linfoblástica aguda Sobrevida global Sobrevida libre de enfermedad Trasplante hematopoyético Factores pronósticos Enfermedad residual medible
dc.subject.lemb.spa.fl_str_mv	Medicina interna Medicina Ciencias médicas Médula ósea (Enfermedades) Inmunoterapia Inmunología clínica Estadística vital Demografía
dc.subject.proposal.spa.fl_str_mv	Ciencias de la salud Leucemia linfoblástica aguda Sobrevida global Sobrevida libre de enfermedad Trasplante hematopoyético Factores pronósticos Enfermedad residual medible
description	Estudio 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.
publishDate	2025
dc.date.accessioned.none.fl_str_mv	2025-06-26T15:46:52Z
dc.date.available.none.fl_str_mv	2025-06-26T15:46:52Z
dc.date.issued.none.fl_str_mv	2025-06-16
dc.type.driver.none.fl_str_mv	info:eu-repo/semantics/masterThesis
dc.type.local.spa.fl_str_mv	Tesis
dc.type.hasversion.none.fl_str_mv	info:eu-repo/semantics/acceptedVersion
dc.type.redcol.none.fl_str_mv	http://purl.org/redcol/resource_type/TM
status_str	acceptedVersion
dc.identifier.uri.none.fl_str_mv	http://hdl.handle.net/20.500.12749/30089
dc.identifier.instname.spa.fl_str_mv	instname:Universidad Autónoma de Bucaramanga - UNAB
dc.identifier.reponame.spa.fl_str_mv	reponame:Repositorio Institucional UNAB
dc.identifier.repourl.spa.fl_str_mv	repourl:https://repository.unab.edu.co
url	http://hdl.handle.net/20.500.12749/30089
identifier_str_mv	instname:Universidad Autónoma de Bucaramanga - UNAB reponame:Repositorio Institucional UNAB repourl:https://repository.unab.edu.co
dc.language.iso.spa.fl_str_mv	spa
language	spa
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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. Brown 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. Brown 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. Greil C, Engelhardt M, Ihorst G, Duque-Afonso J, Shoumariyeh K, Bertz H, et al. Prognostic factors for survival after allogeneic transplantation in acute lymphoblastic leukemia. 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dc.relation.uriapolo.spa.fl_str_mv	https://apolo.unab.edu.co/en/persons/claudia-lucia-sossa-melo
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dc.coverage.spatial.spa.fl_str_mv	Floridablanca (Santander, Colombia)
dc.coverage.temporal.spa.fl_str_mv	2024 - 2025
dc.coverage.campus.spa.fl_str_mv	UNAB Campus Bucaramanga
dc.publisher.grantor.spa.fl_str_mv	Universidad Autónoma de Bucaramanga UNAB
dc.publisher.faculty.spa.fl_str_mv	Facultad Ciencias de la Salud
dc.publisher.program.spa.fl_str_mv	Especialización en Medicina Interna
dc.publisher.programid.none.fl_str_mv	EMIN-1050
institution	Universidad Autónoma de Bucaramanga - UNAB
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spelling	Sossa Melo, Claudia Lucía22544054-3145-4b75-a2c6-dc49fb230dc1Morales Chacón, Katherineec53aad5a-9779-4c0b-a85f-814f9cba2b76Ochoa Vera, Miguel Enriquebf83ca83-93c9-401e-91d3-b424889e868fLuna González , María Lucrecia7f524da3-dbfd-4a5c-9e72-4ea55989230aSossa Pinzón, Luis Alfredo486a57eb-399a-4b49-9616-9e6ae8bbd816Ochoa Vera, Miguel Enrique [0000898465]Luna González, Maria Lucrecia [0001347422]Sossa Melo, Claudia Lucía [0001425704]Morales Chacón, Katherinee [0001618150]Sossa Pinzón, Luis Alfredo [0009-0007-6521-9280]Morales Chacón, Katherinee [0000-0001-6394-6811]Luna González , María Lucrecia [0000-0003-2846-6868]Ochoa Vera, Miguel Enrique [0000-0002-4552-3388]Sossa Melo, Claudia Lucía [0000-0001-9876-222X]Grupo de Investigaciones ClínicasSossa Melo, Claudia Lucía [claudia-lucia-sossa-melo]Luna González , María Lucrecia Lucrecia [maría-lucrecia-luna-gonzález]Ochoa Vera, Miguel Enrique [miguel-enrique-ochoa-vera]Luna González , María Lucrecia [maría-lucrecia-luna-gonzález]Floridablanca (Santander, Colombia)2024 - 2025UNAB Campus Bucaramanga2025-06-26T15:46:52Z2025-06-26T15:46:52Z2025-06-16http://hdl.handle.net/20.500.12749/30089instname:Universidad Autónoma de Bucaramanga - UNABreponame:Repositorio Institucional UNABrepourl:https://repository.unab.edu.coEstudio 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.Planteamiento 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 ........................................................................................................................ 144EspecializaciónThis 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.Modalidad Presencialapplication/pdfspahttp://creativecommons.org/licenses/by-nc-nd/2.5/co/Abierto (Texto Completo)Atribución-NoComercial-SinDerivadas 2.5 Colombiahttp://purl.org/coar/access_right/c_abf2Factores asociados a supervivencia en pacientes con leucemia linfoblástica agudaPrognostic Factors for Survival in Patients with Acute Lymphoblastic LeukemiaEspecialista en Medicina InternaUniversidad Autónoma de Bucaramanga UNABFacultad Ciencias de la SaludEspecialización en Medicina InternaEMIN-1050info:eu-repo/semantics/masterThesisTesisinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/redcol/resource_type/TMInternal medicineMedicineMedical sciencesHealth sciencesAcute lymphoblastic leukemiaOverall survivalDisease-free survivalBlinatumomabPrognostic factorsHematopoietic stem cell transplantationMeasurable residual diseaseBone marrow (Diseases)ImmunotherapyImmunology clinicVital StatisticsDemographyMedicina internaMedicinaCiencias médicasMédula ósea (Enfermedades)InmunoterapiaInmunología clínicaEstadística vitalDemografíaCiencias de la saludLeucemia linfoblástica agudaSobrevida globalSobrevida libre de enfermedadTrasplante hematopoyéticoFactores pronósticosEnfermedad residual medibleEchevarría Martínez Luis Enrique, Guillén Cánovas Ana Mercedes, Márquez Batista Noslen, González Corrales Santa Caridad, Cueto Cos Liliana. 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