Dataset Information

Evidence of spatial clustering of childhood acute lymphoblastic leukemia cases in Greater Mexico City: report from the Mexican Inter-Institutional Group for the identification of the causes of childhood leukemia.

ABSTRACT:

Background

A heterogeneous geographic distribution of childhood acute lymphoblastic leukemia (ALL) cases has been described, possibly, related to the presence of different environmental factors. The aim of the present study was to explore the geographical distribution of childhood ALL cases in Greater Mexico City (GMC).

Methods

A population-based case-control study was conducted. Children <18 years old, newly diagnosed with ALL and residents of GMC were included. Controls were patients without leukemia recruited from second-level public hospitals, frequency-matched by sex, age, and health institution with the cases. The residence address where the patients lived during the last year before diagnosis (cases) or the interview (controls) was used for geolocation. Kulldorff's spatial scan statistic was used to detect spatial clusters (SCs). Relative risks (RR), associated p-value and number of cases included for each cluster were obtained.

Results

A total of 1054 cases with ALL were analyzed. Of these, 408 (38.7%) were distributed across eight SCs detected. A relative risk of 1.61 (p<0.0001) was observed for the main cluster. Similar results were noted for the remaining seven ones. Additionally, a proximity between SCs, electrical installations and petrochemical facilities was observed.

Conclusions

The identification of SCs in certain regions of GMC suggest the possible role of environmental factors in the etiology of childhood ALL.

SUBMITTER: Duarte-Rodriguez DA

PROVIDER: S-EPMC10899509 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

Evidence of spatial clustering of childhood acute lymphoblastic leukemia cases in Greater Mexico City: report from the Mexican Inter-Institutional Group for the identification of the causes of childhood leukemia.

Duarte-Rodríguez David Aldebarán DA Flores-Lujano Janet J McNally Richard J Q RJQ Pérez-Saldivar María Luisa ML Jiménez-Hernández Elva E Martín-Trejo Jorge Alfonso JA Espinoza-Hernández Laura Eugenia LE Medina-Sanson Aurora A Paredes-Aguilera Rogelio R Merino-Pasaye Laura Elizabeth LE Velázquez-Aviña Martha Margarita MM Torres-Nava José Refugio JR Espinosa-Elizondo Rosa Martha RM Amador-Sánchez Raquel R Dosta-Herrera Juan José JJ Mondragón-García Javier Anastacio JA González-Ulibarri Juana Esther JE Martínez-Silva Sofía Irene SI Espinoza-Anrubio Gilberto G Paz-Bribiesca María Minerva MM Salcedo-Lozada Perla P Landa-García Rodolfo Ángel RÁ Ramírez-Colorado Rosario R Hernández-Mora Luis L Santamaría-Ascencio Marlene M López-Loyola Anselmo A Godoy-Esquivel Arturo Hermilo AH García-López Luis Ramiro LR Anguiano-Ávalos Alison Ireri AI Mora-Rico Karina K Castañeda-Echevarría Alejandro A Rodríguez-Jiménez Roberto R Cibrian-Cruz José Alberto JA Solís-Labastida Karina Anastacia KA Cárdenas-Cardos Rocío R López-Santiago Norma N Flores-Villegas Luz Victoria LV Peñaloza-González José Gabriel JG González-Ávila Ana Itamar AI Sánchez-Ruiz Martin M Rivera-Luna Roberto R Rodríguez-Villalobos Luis Rodolfo LR Hernández-Pérez Francisco F Olvera-Durán Jaime Ángel JÁ García-Cortés Luis Rey LR Mata-Rocha Minerva M Sepúlveda-Robles Omar Alejandro OA Bekker-Méndez Vilma Carolina VC Jiménez-Morales Silvia S Meléndez-Zajgla Jorge J Rosas-Vargas Haydée H Vega Elizabeth E Núñez-Enríquez Juan Carlos JC Mejía-Aranguré Juan Manuel JM

Frontiers in oncology 20240214

<h4>Background</h4>A heterogeneous geographic distribution of childhood acute lymphoblastic leukemia (ALL) cases has been described, possibly, related to the presence of different environmental factors. The aim of the present study was to explore the geographical distribution of childhood ALL cases in Greater Mexico City (GMC).<h4>Methods</h4>A population-based case-control study was conducted. Children <18 years old, newly diagnosed with ALL and residents of GMC were included. Controls were pat ...[more]

PMID: 38420017

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Project description:Acute lymphoblastic leukemia (ALL) is the most common cancer in children around the globe. Mexico City has one of the highest incidence rates of childhood leukemia worldwide with 49.5 cases per million children under the age of 15 which is similar to that reported for Hispanic populations living in the United States. In addition, it has been noted a dismal prognosis in Mexican and Hispanic ALL pediatric population. Although ALL, like cancer in general, has its origins in endogenous, exogenous, and genetic factors, several studies have shown that the immune system also plays a deterministic role in cancer development. Among various elements of the immune system, T lymphocytes and NK cells seem to dominate the immune response against leukemia. The aim of the present study was to perform a phenotypic and functional characterization of NK cells in ALL Mexican children at the moment of diagnosis and before treatment initiation. A case-control study was conducted by the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia (MIGICCL). 41 cases were incident ALL children younger than 17 years old and residents of Mexico City. 14 controls were children without leukemia, matched by age and sex with cases. NK cell function was evaluated by degranulation assays towards K562 cells and SLAM-associated protein (SAP) expression was measured by intracellular staining. All assays were performed using peripheral blood mononuclear cells from controls and patients. The results indicate that NK mediated cytotoxicity, measured by CD107a degranulation assays in response to K562 cells, was reduced in ALL patients compared to controls. Interestingly, an impaired NK cell killing of target cells was not equally distributed among ALL patients. In contrast to patients classified as high-risk, standard-risk patients did not display a significant reduction in NK cell-mediated cytotoxicity. Moreover, patients presenting a leukocyte count ≥ 50,000xmm3 displayed a reduction in NK-cell mediated cytotoxicity and a reduction in SAP expression, indicating a positive correlation between a reduced SAP expression and an impaired NK cell-mediated citotoxicity. In the present study it was observed that unlike patients with standard-risk, NK cells from children presenting high-risk ALL, harbor an impaired cytotoxicity towards K562 at diagnosis. In addition, NK cell function was observed to be compromised in patients with a leukocyte count ≥50,000xmm3, where also it was noticed a decreased expression of SAP compared to patients with a leukocyte count <50,000xmm3. These data indicate NK cell-mediated cytotoxicity is not equally affected in ALL patients, nevertheless a positive correlation between low SAP expression and decreased NK cell-mediated cytotoxicity was observed in ALL patients with a leukocyte count ≥50,000xmm3. Finally, an abnormal NK cell-mediated cytotoxicity may represent a prognostic factor for high-risk acute lymphoblastic leukemia.

Project description:Background and aimsPediatric acute lymphoblastic leukemia (ALL) survival rates in low- and middle-income countries are lower due to deficiencies in multilevel factors, including access to timely diagnosis, risk-stratified therapy, and comprehensive supportive care. This retrospective study aimed to analyze outcomes for pediatric ALL at 16 centers in Mexico.MethodsPatients <18 years of age with newly diagnosed B- and T-cell ALL treated between January 2011 and December 2019 were included. Clinical and biological characteristics and their association with outcomes were examined.ResultsOverall, 2,116 patients with a median age of 6.3 years were included. B-cell immunophenotype was identified in 1,889 (89.3%) patients. The median white blood cells at diagnosis were 11.2.5 × 103/mm3. CNS-1 status was reported in 1,810 (85.5%), CNS-2 in 67 (3.2%), and CNS-3 in 61 (2.9%). A total of 1,488 patients (70.4%) were classified as high-risk at diagnosis. However, in 52.5% (991/1,889) of patients with B-cell ALL, the reported risk group did not match the calculated risk group allocation based on National Cancer Institute (NCI) criteria. Fluorescence in situ hybridization (FISH) and PCR tests were performed for 407 (19.2%) and 736 (34.8%) patients, respectively. Minimal residual disease (MRD) during induction was performed in 1,158 patients (54.7%). The median follow-up was 3.7 years. During induction, 191 patients died (9.1%), and 45 patients (2.1%) experienced induction failure. A total of 365 deaths (17.3%) occurred, including 174 deaths after remission. Six percent (176) of patients abandoned treatment. The 5-year event-free survival (EFS) was 58.9% ± 1.7% for B-cell ALL and 47.4% ± 5.9% for T-cell ALL, while the 5-year overall survival (OS) was 67.5% ± 1.6% for B-cell ALL and 54.3% ± 0.6% for T-cell ALL. The 5-year cumulative incidence of central nervous system (CNS) relapse was 5.5% ± 0.6%. For the whole cohort, significantly higher outcomes were seen for patients aged 1-10 years, with DNA index >0.9, with hyperdiploid ALL, and without substantial treatment modifications. In multivariable analyses, age and Day 15 MRD continued to have a significant effect on EFS.ConclusionOutcomes in this multi-institutional cohort describe poor outcomes, influenced by incomplete and inconsistent risk stratification, early toxic death, high on-treatment mortality, and high CNS relapse rate. Adopting comprehensive risk-stratification strategies, evidence-informed de-intensification for favorable-risk patients and optimized supportive care could improve outcomes.

Dataset Information

Evidence of spatial clustering of childhood acute lymphoblastic leukemia cases in Greater Mexico City: report from the Mexican Inter-Institutional Group for the identification of the causes of childhood leukemia.

Background

Methods

Results

Conclusions

Publications

Evidence of spatial clustering of childhood acute lymphoblastic leukemia cases in Greater Mexico City: report from the Mexican Inter-Institutional Group for the identification of the causes of childhood leukemia.

Similar Datasets

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