Search

Introduction: Data on medulloblastoma outcomes and experiences in low- and middle-income countries, especially in Latin America, is limited. This study examines challenges in Mexico's healthcare system, focusing on assessing outcomes for children with medulloblastoma in a tertiary care setting., Methods: A retrospective analysis was conducted, involving 284 patients treated at 21 pediatric oncology centers in Mexico., Results: High-risk patients exhibited markedly lower event-free survival than standard-risk patients (43.5% vs. 78.3%, p<0.001). Influential factors on survival included anaplastic subtype (HR 2.4, p=0.003), metastatic disease (HR 1.9, p=0.001); residual tumor >1.5cm², and lower radiotherapy doses significantly impacted event-free survival (EFS) and overall survival (OS). Platinum-based chemotherapy showed better results compared to the ICE protocol in terms of OS and EFS, which was associated with higher toxicity. Patients under 3 years old displayed notably lower OS and EFS compared to older children (36.1% vs. 55.9%, p=0.01)., Competing Interests: Author DO was employed by ICON PLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Salceda-Rivera, Tejocote-Romero, Osorio, Bellido-Magaña, López-Facundo, Anaya-Aguirre, Ortiz-Morales, Rivera-Luna, Reyes-Gutiérrez, Rivera-Gómez, Velasco-Hidalgo, Cortés-Alva, Lagarda-Arrechea, Arreguín-González, Benito-Reséndiz, Chávez-Gallegos, Pérez-Rivera, Gaytán-Fernández, León-Espitia, Domínguez-Sánchez, Leal-Cavazos, Simón-González, Larios-Farak, Macías-García, García-Espinosa, Guerrero-Maymes, Casillas-Toral and González-Ramella.)

Purpose: Cost containment and efficiency in the provision of health care are primary concerns for health systems that aim to provide affordable, high-quality care. Between 2005 and 2015, Seguro Poplar's Fund against Catastrophic Expenditures (FPGC) funded ALL treatment in Mexico. Before January 1, 2011, FPGC reimbursed a fixed amount per patient according to risk. In 2011, the per capita reimbursement method changed to fee for service. We used this natural experiment to estimate the impact of the reimbursement policy change on average expenditure and quality of care for ALL treatment in Mexico., Methods: We used nationwide reimbursement data from the Seguro Poplar's FPGC from 2005 to 2015. We created a patient cohort to assess 3-year survival and estimate the average reimbursement before and after the fee-for-service policy. We examined survival and expenditure impacts, controlling for patients' and providers' characteristics, including sex, risk (standard and high), the volume of patients served, type of institution (federally funded v other), and level of care. To quantify the impact, we used a regression discontinuity approach., Results: The average reimbursement for standard-risk patients in the 3-year survival cohort was $16,512 US dollars (USD; 95% CI, 16,042 to 17,032) before 2011 and $10,205 USD (95% CI, 4,659 to 12,541) under the fee-for-service reimbursement scheme after 2011. The average annual reimbursement per patient decreased by 136% among high-risk patients. The reduction was also significant for the standard-risk cohort, although the magnitude was substantially smaller (34%)., Conclusion: As Mexico's government is currently restructuring the health system, our study provides evidence of the efficiency and effectiveness of the funding mechanism in the Mexican context. It also serves as a proof of concept for using administrative data to evaluate economic performance and quality of care of publicly funded health programs.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer IO declared a shared affiliation with the author RE-E to the handling editor at the time of review., (Copyright © 2024 Duarte-Rodríguez, Flores-Lujano, McNally, Pérez-Saldivar, Jiménez-Hernández, Martín-Trejo, Espinoza-Hernández, Medina-Sanson, Paredes-Aguilera, Merino-Pasaye, Velázquez-Aviña, Torres-Nava, Espinosa-Elizondo, Amador-Sánchez, Dosta-Herrera, Mondragón-García, González-Ulibarri, Martínez-Silva, Espinoza-Anrubio, Paz-Bribiesca, Salcedo-Lozada, Landa-García, Ramírez-Colorado, Hernández-Mora, Santamaría-Ascencio, López-Loyola, Godoy-Esquivel, García-López, Anguiano-Ávalos, Mora-Rico, Castañeda-Echevarría, Rodríguez-Jiménez, Cibrian-Cruz, Solís-Labastida, Cárdenas-Cardos, López-Santiago, Flores-Villegas, Peñaloza-González, González-Ávila, Sánchez-Ruiz, Rivera-Luna, Rodríguez-Villalobos, Hernández-Pérez, Olvera-Durán, García-Cortés, Mata-Rocha, Sepúlveda-Robles, Bekker-Méndez, Jiménez-Morales, Meléndez-Zajgla, Rosas-Vargas, Vega, Núñez-Enríquez and Mejía-Aranguré.)

Leukemias are the most common type of pediatric cancer around the world. Prognosis has improved during the last decades, and many patients are cured with conventional treatment as chemotherapy; however, many patients still present with a refractory disease requiring additional treatments, including hematopoietic stem cell transplantation. Immunotherapy with monoclonal antibodies or cellular therapy is a promising strategy for treating refractory or relapsed hematological malignancies. Particularly, CAR-T cells have shown clinical efficacy in clinical trials, and different products are now commercially approved by regulatory agencies in the USA and Europe. Many challenges still need to be solved to improve and optimize the potential of these therapies worldwide. Global access to cell therapy is a significant concern, and different strategies are being explored in the middle- and low-income countries. In Mexico, leukemias represent around 50% of total cancer diagnosed in pediatric patients, and the rate of relapsed or refractory disease is higher than reported in other countries, a multi-factorial problem. Although significant progress has been made during the last decades in leukemia diagnosis and treatment, making new therapies available to Mexican patients is a priority, and cell and gene therapies are on the horizon. Efforts are ongoing to make CAR-T cell therapy accessible for patients in Mexico. This article summarizes a general landscape of childhood leukemias in Mexico, and we give a perspective about the current strategies, advances, and challenges ahead to make gene and cell therapies for leukemia clinically available., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bustamante-Ogando, Hernández-López, Galván-Díaz, Rivera-Luna, Fuentes-Bustos, Meneses-Acosta and Olaya-Vargas.)

Background: Some cancer survivors experience difficulties with concentration, attention, and memory; however, there are no studies on neurodevelopment in patients under 5 years of age who are undergoing cancer treatment. Our aim was to evaluate neurodevelopment in cancer patients under 5 years of age using the Early Development Instrument (EDI) test, considering factors such as nutritional status, type of cancer, and treatment effect., Methods: A cross-sectional study was conducted from February 2018 to March 2019. Patients with cancer diagnoses outside the central nervous system in any phase of cancer treatment were included., Results: A total of 45 patients were included. Regarding fine motor skills, 28% of patients with retinoblastoma and 23% of patients with leukemia or lymphoma had a risk of developmental delay compared to 0% of patients with solid tumors (p = 0.025). The final results showed that 19 (42.2%) patients had normal neurodevelopment (gray), 7 (15.5%) had a delay in neurodevelopment (light gray), and 19 (42.2%) had a risk of developmental delay (black). Regarding developmental delay, 52% of patients in the leukemia and lymphoma group, 71% in the retinoblastoma group, and 23% in the solid tumor group presented developmental delay (p = 0.06)., Conclusions: The risk of delay and lag in neurodevelopment is common in cancer patients under 5 years of age undergoing treatment. However, more studies are required to evaluate the effect of treatment on this group of patients as it may be affected by various factors., (Copyright: © 2024 Permanyer.)

Background: Langerhans cell histiocytosis (LCH) is a rare neoplastic disease characterized by clonal proliferation of den-dritic cells. It is Mexico's ninth most frequent malignancy in patients under 18 years of age. The aim of the study was to determine the clinical characteristics, treatment, and survival of Mexican pediatric patients diagnosed with LCH treated from January 2010 to December 2018., Methods: We conducted a retrospective study of LCH using data from 19 accredited hospitals throughout the Mexican Republic. Patients < 18 years who were diagnosed with LCH between January 2010 and December 2018 were included (253 patients) in the study., Results: All patients had a histopathological diagnosis, and extension studies were performed at their treatment centers. The median age at diagnosis was 19 months. The most frequently affected sites included the bone (178 cases; 70%) and the skin (131 cases; 51.7%). Of the patients in Group 1, 48 (42%) had bone marrow involvement, 62 (53%) had splenomegaly, and 39 (34.8%) had liver involvement. Of the patients who underwent chemotherapy treatment, 61.2% exhibited a complete response, and 36 patients (14.2%) relapsed after complete remission. The most frequent sites of relapse were the skin, bone, lymph nodes, and liver. The overall survival rate was 91.3% and was lower for patients in Group 1 (77%) compared with those in Groups 2 (97%) and 3 (100%), p = 0.001., Conclusion: The current report aims to demonstrate the findings of a multicenter study conducted on Mexican children with LCH; consequently, these treatment results for a relatively infrequent disease merit further research., (Copyright: © 2024 Permanyer.)

Acute lymphoblastic leukemia (ALL) is the most common malignancy among Mexican and Hispanic children and the first cause of death by disease in Mexico. We propose a "triple-hit" explanation for the survival gap affecting this population. The first hit can be attributed to epidemiology and social, cultural, and economic burdens. The second hit refers to cancer biology, with a high incidence of unfavorable genetic characteristics associated with an unfavorable response to treatment and, subsequently, poor survival. Finally, the third hit relates to sub-optimal treatment and support. Society and culture, leukemia biology, and treatment approach limitations are key factors that should not be seen apart and must be considered comprehensively in any strategy to improve the prognosis of Mexican and Hispanic children with ALL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rivera-Luna, Perez-Vera, Galvan-Diaz, Velasco-Hidalgo, Olaya-Vargas, Cardenas-Cardos, Aguilar-Ortiz and Ponce-Cruz.)

Leukemia is the most common childhood malignancy in Mexico, representing more than 50% of all childhood cancers. Although treatment leads to a survival of up to 90% in developing countries, in our country, it is less than 65%. Additionally, ~30% of patients relapse with poor prognosis. Alternative splicing plays an important role in transcriptome diversity and cellular biology. This mechanism promotes an increase in the assortment of proteins with potentially distinct functions from a single gene. The proliferating cell nuclear antigen (PCNA) gene encodes two transcripts for the same protein of 261 amino acids, which is associated with several important cellular processes and with several types of cancer. However, the diversity of the transcript variants expressed in this condition is not clear. Then, we used microarray gene expression to identify changes in the exon expression level of PCNA. The data were validated using RT-PCR and Sanger sequencing, and three additional transcripts (PCNA&#95;V3, PCNA&#95;V4, and PCNA&#95;V5) were identified. Computational analyses were used to determine the potential proteins resulting, their structure, and interactions with PCNA native protein and themselves. Additionally, the PCNA transcript variants were inhibited using specific siRNA, determining that their inhibition contributes to the malignant characteristics in vitro. Finally, we quantified the PCNA transcript variants in acute lymphoblastic leukemia samples and identified their expression in this disease. Based on the clinical characteristics, we determined that PCNA&#95;V2 and PCNA&#95;V4 are expressed at significantly low levels in relapsed B-ALL patients. We conclude that the low expression of PCNA&#95;V2 and PCNA&#95;V4 could be a potential molecular marker of relapse in acute lymphoblastic leukemia patients.

Introduction: Over the years, the Hispanic population living in the United States has consistently shown high incidence rates of childhood acute leukemias (AL). Similarly, high AL incidence was previously observed in Mexico City (MC). Here, we estimated the AL incidence rates among children under 15 years of age in MC during the period 2010-2017., Methods: The Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia conducted a study gathering clinical and epidemiological information regarding children newly diagnosed with AL at public health institutions of MC. Crude age incidence rates (cAIR) were obtained. Age-standardized incidence rates worldwide (ASIRw) and by municipalities (ASIRm) were calculated by the direct and indirect methods, respectively. These were reported per million population <15 years of age; stratified by age group, sex, AL subtypes, immunophenotype and gene rearrangements., Results: A total of 903 AL cases were registered. The ASIRw was 63.3 (cases per million) for AL, 53.1 for acute lymphoblastic leukemia (ALL), and 9.4 for acute myeloblastic leukemia. The highest cAIR for AL was observed in the age group between 1 and 4 years (male: 102.34 and female: 82.73). By immunophenotype, the ASIRw was 47.3 for B-cell and 3.7 for T-cell. The incidence did not show any significant trends during the study period. The ASIRm for ALL were 68.6, 66.6 and 62.8 at Iztacalco, Venustiano Carranza and Benito Juárez, respectively, whereas, other municipalities exhibited null values mainly for AML., Conclusion: The ASIRw for childhood AL in MC is among the highest reported worldwide. We observed spatial heterogeneity of rates by municipalities. The elevated AL incidence observed in Mexican children may be explained by a combination of genetic background and exposure to environmental risk factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Flores-Lujano, Duarte-Rodríguez, Jiménez-Hernández, Martín-Trejo, Allende-López, Peñaloza-González, Pérez-Saldivar, Medina-Sanson, Torres-Nava, Solís-Labastida, Flores-Villegas, Espinosa-Elizondo, Amador-Sánchez, Velázquez-Aviña, Merino-Pasaye, Núñez-Villegas, González-Ávila, del Campo-Martínez, Alvarado-Ibarra, Bekker-Méndez, Cárdenas-Cardos, Jiménez-Morales, Rivera-Luna, Rosas-Vargas, López-Santiago, Rangel-López, Hidalgo-Miranda, Vega, Mata-Rocha, Sepúlveda-Robles, Arellano-Galindo, Núñez-Enríquez and Mejía-Aranguré.)

Ph-like subtypes with CRLF2 abnormalities are frequent among Hispano-Latino children with pre-B ALL. Therefore, there is solid ground to suggest that this subtype is frequent in Mexican patients. The genomic complexity of Ph-like subtype constitutes a challenge for diagnosis, as it requires diverse genomic methodologies that are not widely available in diagnostic centers in Mexico. Here, we propose a diagnostic strategy for Ph-like ALL in accordance with our local capacity. Pre-B ALL patients without recurrent gene fusions (104) were classified using a gene-expression profile based on Ph-like signature genes analyzed by qRT-PCR. The expressions of the CRLF2 transcript and protein were determined by qRT-PCR and flow cytometry. The P2RY8::CRLF2 , IGH::CRLF2, ABL1/2 rearrangements, and Ik6 isoform were screened using RT-PCR and FISH. Surrogate markers of Jak2-Stat5/Abl/Ras pathways were analyzed by phosphoflow. Mutations in relevant kinases/transcription factors genes in Ph-like were assessed by target-specific NGS. A total of 40 patients (38.5%) were classified as Ph-like; of these, 36 had abnormalities associated with Jak2-Stat5 and 4 had Abl. The rearrangements IGH::CRLF2, P2RY8::CRLF2 , and iAMP21 were particularly frequent. We propose a strategy for the detection of Ph-like patients, by analyzing the overexpression/genetic lesions of CRLF2 , the Abl phosphorylation of surrogate markers confirmed by gene rearrangements, and Sanger sequencing.

The P2RY8-CRLF2 and IGH-CRLF2 rearrangements induce the overexpression of cytokine receptor-like factor 2 (CRLF2) and have been associated with relapse and poor prognosis in B-cell acute lymphoblastic leukemia (B-ALL). Additionally, they are frequently documented in high-risk Hispanic populations. To better understand the potential causes of the adverse prognosis of childhood B-ALL in Mexico, we analyzed these rearrangements and the CRLF2 mRNA and protein levels in 133 Mexican children with B-ALL. We collected bone marrow samples at diagnosis and evaluated the CRLF2 gene expression by qRT-PCR and the total CRLF2 protein by flow cytometry. P2RY8-CRLF2 and IGH-CRLF2 were detected by RT-PCR and FISH, respectively. The median time of follow-up to determine the prognostic significance of the CRLF2 abnormalities was three years. In 82% of the participants, the mRNA levels correlated with the cell-surface and intracellular CRLF2 protein levels. The P2RY8-CRLF2 rearrangement was present in 31.5% (42/133) of the patients, while the IGH-CRLF2 rearrangement was detected in 13.5% (9/67) of patients with high expression of CRLF2 (6.8% of the total sample). CRLF2 copy number variations (gain) were also detected in 7.5% (5/67) of patients with high protein levels. The overall survival (OS) presented significantly lower rates in patients with high white blood cell count (≥50x10 9 /L) regardless of CRLF2 expression, but high levels of CRLF2 gene expression appears to contribute to the reduction of OS within this group of patients. In conclusion, in our cohort, a high occurrence of CRLF2 abnormalities was documented, particularly the P2RY8-CRLF2 rearrangement, which might represent a characteristic of the Mexican population. Targeted therapy to treat this group of patients could improve OS., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The association between childhood cancer and socioeconomic status has been widely studied. However, none of the results are conclusive. This study aimed to analyze the association between the Human Development Index (HDI) and the acute lymphoblastic leukemia (ALL) incidence in children under the Popular Medical Insurance Care., Methods: We conducted an observational, descriptive, and population-based study covering 55% of the Mexican population (58 million)., Results: The most impoverished states were located in the south east region of Mexico, while the north was more homogeneous, with HDIs varying between 0.73 and 0.79. Our findings emphasize that the metropolitan area of Mexico City and the State of Nuevo Leon have the highest levels of HDI. Regions were graded from I to IV according to their HDIs in ascending order. The HDIs varied from 0.667 to 0.830/100,000 children/year, with a national average of 0.746. The leukemia incidence for regions I, II, III, and IV was 6.12, 6.53, 4.96, and 9.95. An analysis of ALL incidence in Mexico showed significant differences for region IV in comparison with the other regions based on the HDI values (p = 0.0001)., Conclusions: Further in-depth studies, including the economic aspects of the different geographic regions and their ethnographic characteristics, would give a more comprehensive panorama.

The aim of the study was to measure survival of children with acute lymphoblastic leukemia (ALL) under Mexico's public health insurance for the population treated under Seguro Popular . A retrospective cohort study using claims data from Mexico's Seguro Popular program, covering cancer treatment from 2005 to 2015 was conducted. Overall 5-year national and state-specific survival for children with ALL across Mexico who initiated cancer treatment under this program was estimated. From 2005 to 2015, 8,977 children with ALL initiated treatment under Seguro Popular . Under this financing scheme, the annual number of treated children doubled from 535 in 2005 to 1,070 in 2015. The estimates for 5-year overall survival of 61.8% (95%CI 60.8, 62.9) remained constant over time. We observed wide gaps in risk-standardized 5-year overall survival among states ranging from 74.7% to 43.7%. We found a higher risk of mortality for children who received treatment in a non-pediatric specialty hospital (Hazards Ratio, HR = 1.18; 95%CI 1.09, 1.26), facilities without a pediatric oncology/hematology specialist (HR = 2.17; 95%CI 1.62, 2.90), and hospitals with low patient volume (HR = 1.22; 95%CI 1.13, 1.32). In a decade Mexico's Seguro Popular doubled access to ALL treatment for covered children and by 2015 financed the vast majority of estimated ALL cases for that population. While some progress in ALL survival may have been achieved, nationwide 5-year overall survival did not improve over time and did not achieve levels found in comparable countries. Our results provide lessons for Mexico's evolving health system and for countries moving toward universal health coverage.

A high impact of ARID5B SNPs on acute lymphoblastic leukemia (ALL) susceptibility has been described in Hispanic children; therefore, it is relevant to know if they influence the high incidence of childhood-ALL in Mexicans. Seven SNPs (rs10821936, rs10994982, rs7089424, rs2393732, rs2393782, rs2893881, rs4948488) of ARID5B were analyzed in 384 controls and 298 ALL children using genomic DNA and TaqMan probes. The SNPs were analyzed for deviation of Hardy-Weinberg equilibrium; Fisher's exact test was used to compare the genotypic and allelic frequencies between controls and patients. The association between SNPs and ALL susceptibility was calculated, and haplotype and ancestry analyses were conducted. All SNPs were associated with ALL, pre-B ALL, and hyperdiploid-ALL susceptibility (p < 0.05). No association with T-ALL and gene fusions was found (p > 0.05). The seven SNPs were associated with risk of pre-B ALL in younger children; however, rs2393732, rs2393782, rs2893881, and rs4948488 were not associated with susceptibility in older children and adolescents. The CAG haplotype (rs10821936, rs10994982, rs7089424) was strongly associated with ALL risk in our population (p < 0.00001). The frequency of all risk alleles in our ALL, pre-B, and hyperdiploid-ALL patients was higher than that in Hispanic children reported. This is the first report showing the association between rs2393732, rs2393782, and rs4948488 with pre-B hyperdiploid-ALL children. The G allele at rs2893881 confers major risk for pre-B hyperdiploid-ALL in Mexican (OR, 2.29) than in Hispanic children (OR, 1.71). The genetic background of our population could influence the susceptibility to ALL and explain its high incidence in Mexico.

B-cell acute lymphoblastic leukemia is the most commonly diagnosed childhood malignancy worldwide; more than 50% of these cases are diagnosed in Mexico. Although the five-year survival rate is >80%, 30% of patients experience relapse with poor prognosis. Cancer-associated gene expression profiles have been identified in several malignancies, and some transcripts have been used to predict disease prognosis. The human transcriptome is incompletely elucidated; moreover, more than 80% of transcripts can be processed via alternative splicing (AS), which increases transcript and protein diversity. The human transcriptome is divided; coding RNA accounts for 2%, and the remaining 98% is noncoding RNA. Noncoding RNA can undergo AS, promoting the diversity of noncoding transcripts. We designed specific primers to amplify previously reported alternative transcript variants of ZNF695 and showed that six ZNF695 transcript variants are co-expressed in cancer cell lines. The amplicons were sequenced and identified. Additionally, we analyzed the expression of these six transcript variants in bone marrow from B-cell acute lymphoblastic leukemia patients and observed that ZNF695 transcript variants one and three were the predominant variants expressed in leukemia. Moreover, our results showed the co-expression of coding and long noncoding RNA. Finally, we observed that long noncoding RNA ZNF695 expression predicted survival rates.

Anticancer regimens for Hodgkin lymphoma (HL) patients include highly genotoxic drugs that have been very successful in killing tumor cells and providing a 90% disease-free survival at five years. However, some of these treatments do not have a specific cell target, damaging both cancerous and normal cells. Thus, HL survivors have a high risk of developing new primary cancers, both hematologic and solid tumors, which have been related to treatment. Several studies have shown that after treatment, HL patients and survivors present persistent chromosomal instability, including nonclonal chromosomal aberrations. The frequency and type of chromosomal abnormalities appear to depend on the type of therapy and the cell type examined. For example, MOPP chemotherapy affects hematopoietic and germ stem cells leading to long-term genotoxic effects and azoospermia, while ABVD chemotherapy affects transiently sperm cells, with most of the patients showing recovery of spermatogenesis. Both regimens have long-term effects in somatic cells, presenting nonclonal chromosomal aberrations and genomic chaos in a fraction of noncancerous cells. This is a source of karyotypic heterogeneity that could eventually generate a more stable population acquiring clonal chromosomal aberrations and leading towards the development of a new cancer., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background: Feeding difficulties and disorders are a common problem in the pediatric population, which involve a series of deficient behaviors about nutrition processes that can adversely affect psychomotor, psychosocial, and physical development of children. This study aimed to describe the frequency of feeding difficulties or disorders in pediatric patients with cancer., Methods: A prospective study which included 125 children from 1-19 years treated at the Department of Oncology of the Instituto Nacional de Pediatría, Mexico City, was conducted. The diagnosis of eating disorders and feeding difficulties was determined during the first 48 h since admission, and the age of the patient influenced the type of disorder and feeding difficulties., Results: Children older than 11 years presented more frequently an intense resistance of feeding because of discomfort pain (fear of feeding) than younger children (11.4 ± 4.7 vs. 7.4 ± 4.9, p ≤ 0.001). The most frequent alteration associated with malnutrition was loss of appetite (odds ratio [OR]: 8.8, confidence interval [CI] 95% 2.9-26.9, p<0.001), followed by fear of feeding (OR: 3.14, CI 95% 1.24-7.9, p=0.015), and the organic causes showed the highest risk for malnutrition (OR: 3.1, CI 95% 0.98-9.7, p=0.054)., Conclusions: Over 90% of the studied population demonstrated at least one eating disorder or feeding difficulty. The principal effect is inadequate nutritional intake due to limited appetite and fear of feeding, which can result in undernutrition. For this reason, the identification of alterations in nutrition processes should be part of the comprehensive assessment of cancer patients., (Copyright: © 2019 Permanyer.)

In Mexico, due to the high rates of diabetes, overweight, and obesity, there has also been noted an increased newborn weight, which may be contributing to the elevated incidence rate of childhood acute leukemia (AL). We conducted a case-control study in public hospitals of Mexico City aimed to know whether a greater weight at birth is associated with a higher risk of developing leukemia. We included incident cases with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) diagnosed between 2010 and 2015. Controls were frequency-matched to the cases by age, sex, and health institution. Logistic regression analysis was performed adjusting risks by child's sex, overcrowding index, birth order, and mother's age at the time of pregnancy. Adjusted odds ratios (aORs) and 95% confidence intervals were calculated. A total of 1455 cases and 1455 controls were included. An evident association between ALL and child's birthweight ≥2500 g was found (aOR 2.06; 95% CI: 1.59, 2.66) and also, in those with birthweight ≥3500 g (aOR 1.19; 95% CI: 1.00, 1.41). In AML patients with birthweight ≥2500 g and ≥3500 g, an aOR of 1.77 (95% CI: 1.07, 2.94) and 1.42 (95% CI: 1.03-1.95) was observed, respectively. No association was noticed with either type of AL and a birthweight ≥4000 g. To sum up, we found a moderate association between not having a low birthweight and an increased risk of acute leukemias. Birthweight ≥3500 g was also a risk factor for both types of leukemia. This suggests that a greater birthweight may increase the risk of acute leukemias in Mexican children., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Expression of the 6 and 8 dominant-negative Ikaros isoforms in pediatric patients with acute lymphoblastic leukemia has been associated with a high risk of relapse and death; due to these isoforms disrupting the differentiation and proliferation of lymphoid cells. The aim of this study was to know the frequency of Ik6 and Ik8 in 113 Mexican ALL-children treated within the National Popular Medical Insurance Program to determine whether there was an association with relapse-free survival, event-free survival and overall survival, and to assess its usefulness in the initial stratification of patients. The expression of these isoforms was analyzed using specific primer sets and nested RT-PCR. The detected transcripts were classified according to the isoforms's sizes reported. A non-expected band of 300 bp from one patient was analyzed by sequencing. Twenty-six patients expressed Ik6 and/or Ik8 and one of them expressed a variant of Ik8 denominated Ik8-deleted. Although the presence of them was not statistically associated with lower relapse free survival (p = 0.432), event free survival (p = 0.667) or overall survival (p = 0.531), inferior overall survival was observed in patients that expressed these isoforms and showed high or standard risk by age and white blood-cell count at diagnosis. Of the 26 patients Ik6+ and/or Ik8+, 14 did not present adverse events; from them 6 were exclusively Ik6+ and/or Ik8+, and 8 were positive for the other Ikaros isoforms (Ik1, Ik2, Ik5, Ik3A, Ik4, Ik4A, Ik7). In the patients studied, the expression of Ik6 and Ik8 did not constitute an independent prognostic factor for relapse or death related to disease; therefore, they could not be used in the initial risk stratification.

Background: All the children registered at the National Council for the Prevention and Treatment of Childhood Cancer were analyzed. The rationale for this Federal Government Council is to financially support the treatment of all children registered into this system. All patients are within a network of 55 public certified hospitals nationwide., Methods: In the current study, data from 2007 to 2012 are presented for all patients (0-18 years) with a pathological diagnosis of leukemia, lymphoma and solid tumors. The parameters analyzed were prevalence, incidence, mortality, and abandonment rate., Results: A diagnosis of cancer was documented in 14,178 children. The incidence was of 156.9/million/year (2012). The median age was 4.9. The most common childhood cancer is leukemia, which occurs in 49.8% of patients (2007-2012); and has an incidence rate of 78.1/million/year (2012). The national mortality rate was 5.3/100,000 in 2012, however in the group between 15 to 18 years it reaches a level of 8.6., Conclusions: The study demonstrates that there is a high incidence of childhood cancer in Mexico. In particular, the results reveal an elevated incidence and prevalence of leukemia especially from 0 to 4 years. Only 4.7% of these patients abandoned treatment. The clinical outcome for all of the children studied improved since the establishment of this national program.

Background: Worldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in public hospitals in Mexico City., Methods: Included in this study were those children, under 15 years of age and residents of Mexico City, who were diagnosed in 2006 and 2007 with leukemia, as determined by using the International Classification of Childhood Cancer. The average annual incidence rates (AAIR), and the standardized average annual incidence rates (SAAIR) per million children were calculated. We calculated crude, age- and sex-specific incidence rates and adjusted for age by the direct method with the world population as standard. We determined if there were a correlation between the incidence of acute leukemias in the various boroughs of Mexico City and either the number of agricultural hectares, the average number of persons per household, or the municipal human development index for Mexico (used as a reference of socio-economic level)., Results: Although a total of 610 new cases of leukemia were registered during 2006-2007, only 228 fit the criteria for inclusion in this study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3); acute lymphoblastic leukemia (ALL) was the most frequent type of leukemia, constituting 85.1% of the cases (SAAIR: 49.5 per million), followed by acute myeloblastic leukemia at 12.3% (SAAIR: 6.9 per million), and chronic myeloid leukemia at 1.7% (SAAIR: 0.9 per million). The 1-4 years age group had the highest SAAIR for ALL (77.7 per million). For cases of ALL, 73.2% had precursor B-cell immunophenotype (SAAIR: 35.8 per million) and 12.4% had T-cell immunophenotype (SAAIR 6.3 per million). The peak ages for ALL were 2-6 years and 8-10 years. More than half the children (58.8%) were classified as high risk. There was a positive correlation between the average number of persons per household and the incidence of the pre-B immunophenotype (Pearson's r, 0.789; P = 0.02)., Conclusions: The frequency of ALL in Mexico City is among the highest in the world, similar to those found for Hispanics in the United States and in Costa Rica.

In Mexico, Central Nervous System (CNS) tumors are the third most common childhood cancers. Medulloblastoma constitutes 20% of the primary CNS tumors and 40% of all cerebellar tumors, the single most common brain tumor among children. It originates over the external granular layer that normally migrates from the vermis to the surface of the cerebellum hemispheres and from there to the deep portions of the internal granular layer. These tumors infiltrate profusely the cerebellar cortex. The dissemination process can occur through the spinal fluid with seeding along the subarachnoidal space and around the spinal chord They eventually produce metastasis mainly to bone, liver, and bone marrow. There is a group of well identified prognostic factors that are relevant for each individual patient and that can be applied for multidisciplinary treatment purposes. The objective of the present review is to emphasize on new research findings and the overall survival that can be achieved with modern treatment programs.

Leukemia-associated fusion genes are detected in a significant proportion of newly diagnosed cases, where genes encoding transcription factors are usually found at one of the breakpoints. Activated fusion proteins such as Pml-Raralpha have been shown to inhibit cellular differentiation by recruitment of nuclear corepressor complexes, which maintain local histone deacetylase (HDAC) in a variety of hematologic lineage-specific gene promoters. This HDAC-dependent transcriptional repression appears as a common pathway in the development of leukemia and could constitute an important target for new therapeutic agents. Alternatively, the Bcr-Abl oncoprotein shows high tyrosine kinase activity and deregulates signal transduction pathways normally involved in both apoptosis and proliferation. This aberrant activity is affected by signal transduction inhibitors (STIs), which block or prevent the oncogenic pathway. In this review, we shed some light on our understanding of both the reversible transcriptional repression controlled by HDAC and the deregulated Bcr-Abl signal transduction pathway. In addition, the administration of low molecular weight drugs for human leukemia treatment based on this knowledge brings about a significant long-term clinical remission and an acceptable risk of toxic effects that should increase the cure rate.

The congenital immunodeficiency disorders in which the defect has been clearly traced to the stem cell can be cured with allogeneic stem-cell transplantation (SCT) from an unaffected donor. Widespread application of this treatment modality has been tempered by the fact that risk-benefit considerations do not always favor a procedure that carries a significant risk for morbidity and mortality. Some malignant disorders of childhood eventually have to be treated by an autologous or allogeneic SCT, however nonmalignant disorders can also be treated with this approach. This article reviews the current status of SCT for nonmalignant inherited immunodeficiency disorders.