Impact of standardized immunophenotyping and MRD monitoring on early mortality reduction in childhood leukemia: a step towards addressing healthcare disparities in vulnerable populations from Southern Mexico
BackgroundDespite high cure rates for pediatric B-cell acute lymphoblastic leukemia (B-ALL) in high-income countries, early mortality remains unacceptably high in low- and middle-income countries (LMICs), largely due to limited access to risk-adapted therapy and response monitoring. Southern Mexico,...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1614445/full |
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| author | Laura Alfaro-Hernández Laura Alfaro-Hernández Dalia Ramírez-Ramírez Rubí Romo-Rodríguez Karen Ayala-Contreras Ángeles del Campo-Martínez Enrique López-Aguilar Janet Flores Lujano Aldo Allende-López Erika Alarcón-Ruiz Ma Del Rocio Banos-Lara Ma Del Rocio Banos-Lara Diana Casique-Aguirre Diana Casique-Aguirre Jesús Elizarrarás-Rivas Javier Antonio López-Aquino Miguel Ángel Garrido-Hernández Daniela Olvera-Caraza Vanessa Terán-Cerqueda Juan Carlos Solís-Poblano Pierre Mitchel Aristil-Chery Enoch Alvarez-Rodríguez Enoch Alvarez-Rodríguez Wilfrido Herrera-Olivares Lénica Anahí Chavez-Aguilar Aquilino Márquez-Toledo Lena Sarahi Cano-Cuapio Nuria Citlalli Luna-Silva Maria Angélica Martínez-Martell Anabel Beatriz Ramirez-Ramirez Juan Carlos Rodríguez-Espinosa Daniela Medina-León Roberto Rodríguez-Díaz Minerva Mata-Rocha Amanda Idaric Olivares-Sosa Haydeé Rosas-Vargas Juan Manuel Mejia-Arangure Juan Manuel Mejia-Arangure Lourdes Millán-Pérez-Peña Rosana Pelayo Rosana Pelayo Juan Carlos Núñez-Enríquez |
| author_facet | Laura Alfaro-Hernández Laura Alfaro-Hernández Dalia Ramírez-Ramírez Rubí Romo-Rodríguez Karen Ayala-Contreras Ángeles del Campo-Martínez Enrique López-Aguilar Janet Flores Lujano Aldo Allende-López Erika Alarcón-Ruiz Ma Del Rocio Banos-Lara Ma Del Rocio Banos-Lara Diana Casique-Aguirre Diana Casique-Aguirre Jesús Elizarrarás-Rivas Javier Antonio López-Aquino Miguel Ángel Garrido-Hernández Daniela Olvera-Caraza Vanessa Terán-Cerqueda Juan Carlos Solís-Poblano Pierre Mitchel Aristil-Chery Enoch Alvarez-Rodríguez Enoch Alvarez-Rodríguez Wilfrido Herrera-Olivares Lénica Anahí Chavez-Aguilar Aquilino Márquez-Toledo Lena Sarahi Cano-Cuapio Nuria Citlalli Luna-Silva Maria Angélica Martínez-Martell Anabel Beatriz Ramirez-Ramirez Juan Carlos Rodríguez-Espinosa Daniela Medina-León Roberto Rodríguez-Díaz Minerva Mata-Rocha Amanda Idaric Olivares-Sosa Haydeé Rosas-Vargas Juan Manuel Mejia-Arangure Juan Manuel Mejia-Arangure Lourdes Millán-Pérez-Peña Rosana Pelayo Rosana Pelayo Juan Carlos Núñez-Enríquez |
| author_sort | Laura Alfaro-Hernández |
| collection | DOAJ |
| description | BackgroundDespite high cure rates for pediatric B-cell acute lymphoblastic leukemia (B-ALL) in high-income countries, early mortality remains unacceptably high in low- and middle-income countries (LMICs), largely due to limited access to risk-adapted therapy and response monitoring. Southern Mexico, a region marked by socioeconomic vulnerability, is emblematic of this disparity. In 2022 the Childhood Cancer Cytomics Laboratory (CCCL) started the implementation of standardized protocols for immunophenotyping and measurable residual disease (MRD) monitoring of B-ALL patients from this region.ObjectiveTo evaluate the impact of implementing standardized immunophenotyping and MRD monitoring on early mortality in children with B-ALL treated in public hospitals in southern Mexico.MethodsA prospective cohort study was conducted between 2022 and 2024. Before initiating CCCL activities, public hospitals were invited to participate, and standardized protocols for sample collection, handling, and transportation were implemented across all participating sites. A total of 298 children newly diagnosed with B-ALL were enrolled and followed throughout treatment. Patients were stratified based on whether immunophenotyping and MRD monitoring were performed at the CCCL. MRD was assessed at the end of induction (EOI) therapy using standardized EuroFlow-based flow cytometry protocols. Simultaneously, early mortality—defined as death occurring within the first year after diagnosis—was evaluated. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were estimated using multivariable Cox regression, with p-values < 0.05 considered statistically significant.ResultsEarly mortality was significantly lower among patients who underwent MRD monitoring at the CCCL (10.8%) compared to those who did not (24.8%, p<0.01). One-year overall survival was also higher in patients evaluated at the CCCL (89.6% vs. 75.2%, p<0.001). In the multivariable Cox regression analysis, patients who underwent MRD monitoring at the CCCL showed a significantly lower risk of early mortality during the first year of treatment (adjusted hazard ratio [aHR] 0.41; 95% CI: 0.22–0.77; p < 0.01), after adjusting for sex, NCI risk classification, treatment abandonment, and early relapse. MRD positivity was associated with a CD34+ ProB immunophenotype, suggesting a more treatment-resistant leukemic profile.ConclusionCentralized, standardized MRD monitoring at the CCCL was associated with a reduction in early mortality and improved one-year survival in children with B-ALL from a socioeconomically vulnerable population. These findings demonstrate the clinical value and feasibility of implementing MRD-informed response assessment in LMICs and highlight the potential of centralized diagnostic platforms to reduce survival disparities in childhood leukemia. |
| format | Article |
| id | doaj-art-c0bf472f580144888fc50f022a50c6ec |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-c0bf472f580144888fc50f022a50c6ec2025-08-20T03:58:48ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-07-011510.3389/fonc.2025.16144451614445Impact of standardized immunophenotyping and MRD monitoring on early mortality reduction in childhood leukemia: a step towards addressing healthcare disparities in vulnerable populations from Southern MexicoLaura Alfaro-Hernández0Laura Alfaro-Hernández1Dalia Ramírez-Ramírez2Rubí Romo-Rodríguez3Karen Ayala-Contreras4Ángeles del Campo-Martínez5Enrique López-Aguilar6Janet Flores Lujano7Aldo Allende-López8Erika Alarcón-Ruiz9Ma Del Rocio Banos-Lara10Ma Del Rocio Banos-Lara11Diana Casique-Aguirre12Diana Casique-Aguirre13Jesús Elizarrarás-Rivas14Javier Antonio López-Aquino15Miguel Ángel Garrido-Hernández16Daniela Olvera-Caraza17Vanessa Terán-Cerqueda18Juan Carlos Solís-Poblano19Pierre Mitchel Aristil-Chery20Enoch Alvarez-Rodríguez21Enoch Alvarez-Rodríguez22Wilfrido Herrera-Olivares23Lénica Anahí Chavez-Aguilar24Aquilino Márquez-Toledo25Lena Sarahi Cano-Cuapio26Nuria Citlalli Luna-Silva27Maria Angélica Martínez-Martell28Anabel Beatriz Ramirez-Ramirez29Juan Carlos Rodríguez-Espinosa30Daniela Medina-León31Roberto Rodríguez-Díaz32Minerva Mata-Rocha33Amanda Idaric Olivares-Sosa34Haydeé Rosas-Vargas35Juan Manuel Mejia-Arangure36Juan Manuel Mejia-Arangure37Lourdes Millán-Pérez-Peña38Rosana Pelayo39Rosana Pelayo40Juan Carlos Núñez-Enríquez41Laboratorio de Citómica del Cáncer Infantil, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, MexicoFacultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, MexicoLaboratorio de Citómica del Cáncer Infantil, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, MexicoLaboratorio de Citómica del Cáncer Infantil, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, MexicoLaboratorio de Citómica del Cáncer Infantil, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, MexicoCoordinación de Atención Oncológica, Instituto Mexicano del Seguro Social, Mexico City, MexicoCoordinación de Atención Oncológica, Instituto Mexicano del Seguro Social, Mexico City, MexicoUnidad de Investigación Médica en Epidemiología Clínica, Unidad Médica de Alta Especialidad (UMAE) Hospital de Pediatría “Dr. Silvestre Frenk Freund”, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, MexicoUnidad de Investigación Médica en Epidemiología Clínica, Unidad Médica de Alta Especialidad (UMAE) Hospital de Pediatría “Dr. Silvestre Frenk Freund”, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, MexicoTecnológico Nacional de México, Instituto Tecnológico de Ciudad de Madero, Ciudad Madero, Tamaulipas, MexicoFacultad de Medicina, Universidad Popular Autónoma del Estado de Puebla, Puebla, MexicoCentro de Investigación Oncológica Una Nueva Esperanza, Universidad Popular Autónoma del Estado de Puebla, Puebla, MexicoLaboratorio de Citómica del Cáncer Infantil, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, MexicoSecretaría de Ciencia, Humanidades, Tecnología e Innovación (Secihti), Mexico City, MexicoCoordinación de Investigación en Salud, Instituto Mexicano del Seguro Social, Oaxaca, Mexico0Coordinación Clínica de Educación e Investigación en Salud de la Unidad de Medicina Familiar (UMF) No. 1, Instituto Mexicano del Seguro Social, Oaxaca, Mexico1Servicio de Oncohematología Pediátrica, Hospital para el Niño Poblano, Secretaria de Salud (SS), Puebla, Mexico1Servicio de Oncohematología Pediátrica, Hospital para el Niño Poblano, Secretaria de Salud (SS), Puebla, Mexico2Servicio de Oncohematología Pediátrica, Instituto Mexicano del Seguro (IMSS) Unidad Médica de Alta Especialidad (UMAE) Centro Médico Nacional (CMN) Hospital de Especialidades Dr. Manuel Ávila Camacho, Puebla, Mexico3Servicio de Hematología, Instituto Mexicano del Seguro (IMSS) Unidad Médica de Alta Especialidad (UMAE) Centro Médico Nacional (CMN) Hospital de Especialidades Dr. Manuel Ávila Camacho, Puebla, Mexico4Departamento de Enseñanza e Investigación, Instituto de Seguridad y Servicios Sociales de los Trabajadores al Servicio de los Poderes del Estado de Puebla (ISSSTEP), Puebla, Mexico5Servicio de Oncohematología Pediátrica, Instituto de Seguridad y Servicios Sociales de los Trabajadores al Servicio de los Poderes del Estado de Puebla (ISSSTEP), Puebla, Mexico6Servicio de Hematología Pediátrica, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), Puebla, Mexico7Servicio de Oncohematología, Hospital General del Sur Dr. Eduardo Vázquez Navarro, Secretaria de Salud (SS), Puebla, Mexico6Servicio de Hematología Pediátrica, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), Puebla, Mexico8Departamento de Pediatría, Hospital Universitario de Puebla (BUAP), Puebla, Mexico9Servicio de Oncología Pediátrica, Hospital Infantil de Tlaxcala, Secretaria de Salud (SS), Tlaxcala, Mexico0Servicio de Hemato-Oncología Pediátrica, Hospital de la Niñez Oaxaqueña “Dr. Guillermo Zárate Mijangos”, Secretaria de Salud y Servicios de Salud Oaxaca (SSO), Oaxaca, Mexico0Servicio de Hemato-Oncología Pediátrica, Hospital de la Niñez Oaxaqueña “Dr. Guillermo Zárate Mijangos”, Secretaria de Salud y Servicios de Salud Oaxaca (SSO), Oaxaca, Mexico1Servicio de Oncocrean, Hospital General de Zona 01 “Dr. Demetrio Mayoral Pardo” Instituto Mexicano del Seguro Social (IMSS), Oaxaca, MexicoCentro de Investigación Oncológica Una Nueva Esperanza, Universidad Popular Autónoma del Estado de Puebla, Puebla, Mexico2Facultad Mexicana De Medicina Universidad La Salle, Mexico City, Mexico3Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), México City, Mexico4Unidad de Investigación Médica en Genética Humana, Unidad Médica de Alta Especialidad (UMAE) Hospital de Pediatría “Dr. Silvestre Frenk Freund”, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico5Dirección de Educación e Investigación, Unidad Médica de Alta Especialidad (UMAE) Hospital de Pediatría “Dr. Silvestre Frenk Freund”, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico4Unidad de Investigación Médica en Genética Humana, Unidad Médica de Alta Especialidad (UMAE) Hospital de Pediatría “Dr. Silvestre Frenk Freund”, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico3Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), México City, Mexico6Laboratorio de Genómica Funcional del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico7Laboratorio de Bioquímica y Biología Molecular, Centro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Puebla, MexicoLaboratorio de Citómica del Cáncer Infantil, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, Mexico8Unidad de Educación e Investigación, Instituto Mexicano del Seguro Social, Mexico City, Mexico9División de Investigación en Salud, Unidad Médica de Alta Especialidad (UMAE) Hospital de Pediatría “Dr. Silvestre Frenk Freund”, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, MexicoBackgroundDespite high cure rates for pediatric B-cell acute lymphoblastic leukemia (B-ALL) in high-income countries, early mortality remains unacceptably high in low- and middle-income countries (LMICs), largely due to limited access to risk-adapted therapy and response monitoring. Southern Mexico, a region marked by socioeconomic vulnerability, is emblematic of this disparity. In 2022 the Childhood Cancer Cytomics Laboratory (CCCL) started the implementation of standardized protocols for immunophenotyping and measurable residual disease (MRD) monitoring of B-ALL patients from this region.ObjectiveTo evaluate the impact of implementing standardized immunophenotyping and MRD monitoring on early mortality in children with B-ALL treated in public hospitals in southern Mexico.MethodsA prospective cohort study was conducted between 2022 and 2024. Before initiating CCCL activities, public hospitals were invited to participate, and standardized protocols for sample collection, handling, and transportation were implemented across all participating sites. A total of 298 children newly diagnosed with B-ALL were enrolled and followed throughout treatment. Patients were stratified based on whether immunophenotyping and MRD monitoring were performed at the CCCL. MRD was assessed at the end of induction (EOI) therapy using standardized EuroFlow-based flow cytometry protocols. Simultaneously, early mortality—defined as death occurring within the first year after diagnosis—was evaluated. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were estimated using multivariable Cox regression, with p-values < 0.05 considered statistically significant.ResultsEarly mortality was significantly lower among patients who underwent MRD monitoring at the CCCL (10.8%) compared to those who did not (24.8%, p<0.01). One-year overall survival was also higher in patients evaluated at the CCCL (89.6% vs. 75.2%, p<0.001). In the multivariable Cox regression analysis, patients who underwent MRD monitoring at the CCCL showed a significantly lower risk of early mortality during the first year of treatment (adjusted hazard ratio [aHR] 0.41; 95% CI: 0.22–0.77; p < 0.01), after adjusting for sex, NCI risk classification, treatment abandonment, and early relapse. MRD positivity was associated with a CD34+ ProB immunophenotype, suggesting a more treatment-resistant leukemic profile.ConclusionCentralized, standardized MRD monitoring at the CCCL was associated with a reduction in early mortality and improved one-year survival in children with B-ALL from a socioeconomically vulnerable population. These findings demonstrate the clinical value and feasibility of implementing MRD-informed response assessment in LMICs and highlight the potential of centralized diagnostic platforms to reduce survival disparities in childhood leukemia.https://www.frontiersin.org/articles/10.3389/fonc.2025.1614445/fullpediatric B-cell acute lymphoblastic leukemiaimmunophenotypingmeasurable residual disease (MRD)early-mortalitylow-and middle -income countries |
| spellingShingle | Laura Alfaro-Hernández Laura Alfaro-Hernández Dalia Ramírez-Ramírez Rubí Romo-Rodríguez Karen Ayala-Contreras Ángeles del Campo-Martínez Enrique López-Aguilar Janet Flores Lujano Aldo Allende-López Erika Alarcón-Ruiz Ma Del Rocio Banos-Lara Ma Del Rocio Banos-Lara Diana Casique-Aguirre Diana Casique-Aguirre Jesús Elizarrarás-Rivas Javier Antonio López-Aquino Miguel Ángel Garrido-Hernández Daniela Olvera-Caraza Vanessa Terán-Cerqueda Juan Carlos Solís-Poblano Pierre Mitchel Aristil-Chery Enoch Alvarez-Rodríguez Enoch Alvarez-Rodríguez Wilfrido Herrera-Olivares Lénica Anahí Chavez-Aguilar Aquilino Márquez-Toledo Lena Sarahi Cano-Cuapio Nuria Citlalli Luna-Silva Maria Angélica Martínez-Martell Anabel Beatriz Ramirez-Ramirez Juan Carlos Rodríguez-Espinosa Daniela Medina-León Roberto Rodríguez-Díaz Minerva Mata-Rocha Amanda Idaric Olivares-Sosa Haydeé Rosas-Vargas Juan Manuel Mejia-Arangure Juan Manuel Mejia-Arangure Lourdes Millán-Pérez-Peña Rosana Pelayo Rosana Pelayo Juan Carlos Núñez-Enríquez Impact of standardized immunophenotyping and MRD monitoring on early mortality reduction in childhood leukemia: a step towards addressing healthcare disparities in vulnerable populations from Southern Mexico Frontiers in Oncology pediatric B-cell acute lymphoblastic leukemia immunophenotyping measurable residual disease (MRD) early-mortality low-and middle -income countries |
| title | Impact of standardized immunophenotyping and MRD monitoring on early mortality reduction in childhood leukemia: a step towards addressing healthcare disparities in vulnerable populations from Southern Mexico |
| title_full | Impact of standardized immunophenotyping and MRD monitoring on early mortality reduction in childhood leukemia: a step towards addressing healthcare disparities in vulnerable populations from Southern Mexico |
| title_fullStr | Impact of standardized immunophenotyping and MRD monitoring on early mortality reduction in childhood leukemia: a step towards addressing healthcare disparities in vulnerable populations from Southern Mexico |
| title_full_unstemmed | Impact of standardized immunophenotyping and MRD monitoring on early mortality reduction in childhood leukemia: a step towards addressing healthcare disparities in vulnerable populations from Southern Mexico |
| title_short | Impact of standardized immunophenotyping and MRD monitoring on early mortality reduction in childhood leukemia: a step towards addressing healthcare disparities in vulnerable populations from Southern Mexico |
| title_sort | impact of standardized immunophenotyping and mrd monitoring on early mortality reduction in childhood leukemia a step towards addressing healthcare disparities in vulnerable populations from southern mexico |
| topic | pediatric B-cell acute lymphoblastic leukemia immunophenotyping measurable residual disease (MRD) early-mortality low-and middle -income countries |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1614445/full |
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