Implementation of a roadmap for the comprehensive diagnosis, follow-up, and research of childhood leukemias in vulnerable regions of Mexico: results from the PRONAII Strategy

Abstract

The main objective of the National Project for Research and Incidence of Childhood Leukemias is to reduce early mortality rates for these neoplasms in the vulnerable regions of Mexico. This project was conducted in the states of Oaxaca, Puebla, and Tlaxcala. A key strategy of the project is the implementation of an effective roadmap to ensure that leukemia patients are the target of maximum benefit of interdisciplinary collaboration between researchers, clinicians, surveyors, and laboratories. This strategy guarantees the comprehensive management of diagnosis and follow-up samples of pediatric patients with leukemia, centralizing, managing, and analyzing the information collected. Additionally, it allows for a precise diagnosis and monitoring of the disease through immunophenotype and measurable residual disease (MRD) studies, enhancing research and supporting informed clinical decisions for the first time in these regions through a population-based study. This initiative has significantly improved the diagnostic capacity of leukemia in girls, boys, and adolescents in the regions of Oaxaca, Puebla, and Tlaxcala, providing comprehensive, high-quality care with full coverage in the region. Likewise, it has strengthened collaboration between health institutions, researchers, and professionals in the sector, which contributes to reducing the impact of the disease on the community.

Keywords: Mexico; childhood leukemias; diagnosis; measurable residual disease (MRD); vulnerable regions.

Figure 1

A roadmap for leukemia in vulnerable regions: Custody from clinical suspicion to comprehensive treatment. The process was structured into seven crucial phases that guaranteed the meticulous treatment of each leukemia patient sample. Furthermore, these stages ensure the adequate concentration, management, and analysis of the information produced. This approach supports accurate patient follow-up, focused research, and data-driven clinical decision making. In Puebla, the hospitals that collaborated in this process are the Unidad Médica de Alta Especialidad Hospital de Especialidades “Dr. Manuel Ávila Camacho” Hospital of the Instituto Mexicano del Seguro social (IMSS), the Hospital para el Niño Poblano (HNP) of the Ministry of Health, the Instituto de Seguridad y Servicios Sociales para los Trabajadores del Estado (ISSSTE), the Instituto de Seguridad y Servicios Sociales para los Trabajadores del Estado de Puebla (ISSSTEP) and the Hospital General del Sur. In Tlaxcala, collaboration came from the Hospital Infantil de Tlaxcala (HIT). In Oaxaca, the Hospital de la Niñez Oaxaqueña (HNO) of Instituto de Salud para el Bienestar (INSABI), and the Hospital General de Zona No. 1 (HGZ01) of the IMSS Oaxaca actively participated.

Figure 2

Immunophenotyping of acute leukemia using flow cytometry. This figure presents illustrative cases of various hematopoietic populations, including residual normal and pathological hematopoietic cells detectable in bone marrow samples from pediatric patients with different subtypes of acute leukemia, including ProB ALL, ProB-PreB ALL, PreB ALL, T-cell precursor acute lymphoblastic leukemia (T ALL), acute myeloid leukemia (AML), and detectable B ALL MRD. At diagnosis, dot plots of AL cases showed a blast population comprising more than 20% of nucleated cells, while in the B-ALL MRD test a representative plot detecting only 0.01% of blast is showed. Colors corresponding to each cell population are indicated at the bottom of the figure.

Figure 3

Diagnosis and distribution of acute leukemia in Mexican childhood patients. (A) Donut chart detailing all the tests. Inner ring: total and minimal residual disease (MRD) diagnostic tests; second ring: percentage of positive and negative results; third ring: classification of acute leukemia. (B) Breakdown of the diagnostic tests performed in the states of Puebla, Oaxaca, and Tlaxcala, showing the frequency according to leukemia classification. (C) Radial graph showing the distribution of cases according to sex and acute leukemia subtype. (D) Histogram illustrating the number of pediatric acute leukemia cases and their distribution according to age and sex at the time of diagnosis.

Figure 4

PRONAII Cell Repository of Childhood Leukemia in Mexican Patients: (A) A total of 5,130 samples from patients with Oaxaca, Puebla, and Tlaxcala, in which different components of the bone marrow (blue graph) and peripheral blood (orange graph) were preserved, as well as urine samples (yellow graph). Stored components: RNA, ribonucleic acid; plasma, serum; WBM, whole bone marrow; MSC, mesenchymal stromal cells; MNC, mononuclear cells; BF, buffer-free leukocytes; LB, Leukocytes in Lysis Buffer; FBS, leukocytes stored in fetal bovine serum (FBS). (B) MSCs were obtained from 128 patients. These include patients with ALL and AML, both at diagnosis and at the minimal residual disease (MDR) stage, as well as those with mixed-phenotype acute leukemia (MPAL) and myelodysplastic syndromes (MDS) at diagnosis. Additionally, MSCs from patients with a negative diagnosis of acute leukemia (non-AL) were stored. (C) Different research projects have received 515 specimens from patients.