Role of Genetic Polymorphisms -238 G>A and -308 G>A, and Serum TNF-α Levels in a Cohort of Mexican Pediatric Neuroblastoma Patients: Preliminary Study.

The results of in vitro and in vivo studies have shown the pro-tumor effects of TNF-α, and this cytokine's increased expression is associated with poor prognosis in patients with some types of cancer. Our study objective was to evaluate the possible association of TNF-α genetic polymorphisms and serum levels with susceptibility and prognosis in a cohort of Mexican patients with NB. We performed PCR-RFLP and ELISA methods to analyze the genetics of these SNPs and determine serum concentrations, respectively. The distribution of the -308 G>A and -238 G>A polymorphisms TNFα genotypes was considerably different between patients with NB and the control group. The SNP rs1800629 GG/GA genotypes were associated with a decreased risk of NB (OR = 0.1, 95% CI = 0.03-0.393, p = 0.001) compared with the AA genotype, which was associated with susceptibility to NB (OR = 2.89, 95% CI = 1.45-5.76, p = 0.003) and related to unfavorable histology and high-risk NB. The rs361525 polymorphism GG genotype was associated with a lower risk of developing NB compared with the GA and AA genotypes (OR = 0.2, 95% CI = 0.068-0.63, p = 0.006). Circulating TNF-α serum concentrations were significantly different (p < 0.001) between patients with NB and healthy controls; however, we found no relationship between the analyzed TNF-α serum levels and SNP genotypes. We found associations between the rs1800629AA genotype and lower event-free survival (p = 0.026); SNP rs361525 and TNF-α levels were not associated with survival in patients with NB. Our results suggest the TNF-α SNP rs1800629 as a probable factor of NB susceptibility. The -308 G/A polymorphism AA genotype has a probable role in promoting NB development and poor prognosis associated with unfavorable histology, high-risk tumors, and lower EFS in Mexican patients with NB. It should be noted that it is important to conduct research on a larger scale, through inter-institutional studies, to further evaluate the contribution of TNF-α genetic polymorphisms to the risk and prognosis of NB.

CRLF2 and IKZF1 abnormalities in childhood hematological malignancies other than B-cell Acute Lymphoblastic Leukemia.

Rearrangements and overexpression of CRLF2 are hallmarks of poor outcomes in BCR::ABL1-like B-ALL, and CRLF2 overexpression is a high-risk marker in T-ALL. However, CRLF2 alterations in pediatric hematologic malignancies other than B-ALL have not been reported. In this study, we analyzed the CRLF2 overexpression, rearrangements (P2RY8::CRLF2 and IGH::CRLF2), activation (pSTAT5 and pERK), and the expression of dominant-negative IKZF1 isoforms (Ik6 and Ik8), implied in CRLF2 dysregulation, in 16 pediatric patients (AML, n = 9; T-ALL, n = 3; LBL, n = 2; HL, n = 1; cytopenia, n = 1). A high frequency of CRLF2 rearrangements and overexpression was found in the 16 patients: 28.6% (4/14) showed CRLF2 overexpression, 93.8% (15/16) were positive for CRLF2 total protein (cell-surface and/or cytoplasmic), while 62.5% (10/16) were positive for P2RY8::CRLF2 and 12.6% (2/16) for IGH::CRLF2. In addition, 43.8% (7/16) expressed Ik6 and Ik8 isoforms. However, only a few patients were positive for the surrogate markers pSTAT5 (14.3%; 2/14) and pERK (21.4%; 3/14).

Germline mutations in pediatric cancer cohort with mixed-ancestry Mexicans.

BACKGROUND: Childhood cancer is one of the primary causes of disease-related death in 5- to 14-year-old children and currently no prevention strategies exist to reduce the incidence of this disease. Childhood cancer has a larger hereditary component compared with cancer in adults. Few genetic studies have been conducted on children with cancer. Additionally, Latin American populations are underrepresented in genomic studies compared with other populations. Therefore, the aim of this study is to analyze germline mutations in a group of mixed-ancestry Mexican pediatric patients with solid and hematological cancers. METHODS: We analyzed genetic variants from 40 Mexican childhood cancer patients and their relatives. DNA from saliva or blood samples was used for whole-exome sequencing. All variants were identified following GATK best practices. RESULTS: We found that six patients (15%) were carriers of germline mutations in CDKN2A, CHEK2, DICER1, FANCA, MSH6, MUTYH, NF1, and SBDS cancer predisposition genes, and additional new variants predicted to be deleterious by in silico algorithms. A population genetics analysis detected five components consistent with the demographic models assumed for modern mixed-ancestry Mexicans. CONCLUSIONS: This report identifies potential genetic risk factors and provides a better understanding of the underlying mechanisms of childhood cancer in this population.

Impairments in fine motor skills in children with Acute Lymphoblastic Leukaemia. A cross-sectional study.

AIM: We evaluated fine motor skills; precision, motor integration, manual dexterity, and upper-limb coordination according to sex and risk stratification in children with Acute Lymphoblastic Leukaemia (ALL). METHODS: We evaluated twenty-nine children in the maintenance phase aged 6 to 12 years with the Bruininks-Oseretsky Test of Motor Proficiency-second edition (BOT-2), and sex and age-specific norm values of BOT-2 were used to compare our results. RESULTS: We found lower scores on the upper-limb coordination subtest, p = 0.003 and on the manual coordination composite, p = 0.008, than normative values. Most boys performed "average" on both the subtests and the composites, but girls showed lower scores with a mean difference of 7.69 (95%CI; 2.24 to 3.14), p = 0.009. Girls' scale scores on the upper-limb coordination subtest were lower than normative values, with mean difference 5.08 (95%CI; 2.35 to 7.81), p = 0.006. The mean standard score difference in high-risk patients was lower than normative on the manual coordination composite, 8.18 (95%CI; 2.26 to 14.1), p = 0.015. High-risk children also performed below the BOT-2 normative on manual dexterity 2.82 (95%CI; 0.14 to 5.78), p = 0.035 and upper limb coordination subtest 4.10 (95%CI; 1.13 to 7.05), p = 0.028. We found a decrease in fine motor precision in children with a higher BMI, rho= -0.87, p = 0.056 and a negative correlation between older age and lower manual dexterity, r= -0.41 p = 0.026; however, we did not find any correlation with the weeks in the maintenance phase. CONCLUSIONS: Fine motor impairments are common in children with ALL in the maintenance phase; it is important to identify these impairments to early rehabilitation.

Characterization of Philadelphia-like Pre-B Acute Lymphoblastic Leukemia: Experiences in Mexican Pediatric Patients.

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.

Mortality in children with cancer and SARS-CoV-2 in Latin America: A systematic review.

The new COVID-19 disease is caused by a novel coronavirus (SARS-CoV-2), that probably originated in Wuhan, China, and has currently infected 505,817,953 people and caused 6,213,876 deaths in the world. On the American continent, 152,265,980 cases and 2,717,108 deaths have been reported to WHO (World Health Organization). The Latin America and the Caribbean (LAC) region presents an epidemiological challenge due to its population's heterogeneity and socioeconomic inequality. A particularly vulnerable population is that of children with cancer, and their mortality from COVID-19 has been reported to be 3.6% globally. This work aimed to study the lethality of SARS-CoV-2 infection in children with cancer in the Latin American region. Our objective was to systematically review published scientific literature and search hospital databases in Latin America to explore mortality in this region. A median of mortality of 9.8% was found in the articles analyzed. In addition, we collected five databases from Latin American hospitals. We concluded that there was an underestimation in the mortality registry of this group of patients in the analyzed region. Therefore, although the causes are unknown, it is necessary to strengthen the case-reporting system to determine the reality in complex and particular areas such as Latin America.

High occurrence of CRLF2 abnormalities in Mexican children with B-cell acute lymphoblastic leukemia.

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 (≥50x109/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.

Decision-Making at End-of-Life for Children With Cancer: A Systematic Review and Meta-Bioethical Analysis.

BACKGROUND: Evidence shows that medical education includes a variety of basic and clinical skills. Ethical and human values are not typically considered in medical school curricula, and this is evident in medical practice in certain scenarios such as decision-making at pediatric cancer patients' end of life. METHODS: This study explores a bioethical approach to address complex decision-making at the end of life in children and adolescents with cancer. We are a cross-functional group of scientists from several academic disciplines who conducted a systematic review of the literature using our newly developed meta-bioethical analysis and synthesis of findings. The search was carried out in five databases, resulting in 10 research papers. Following quality screening, seven articles were ultimately selected for further analysis. RESULTS: Our focus is on the state of the art to better understand the bioethical deliberation at the end of life in pediatric oncology. Here, we report a systematic review that includes (i) classification of the screened articles by the type of decision-making they use, ii) the system values that are at the core of the decision-making at the end of life, and iii) bioethical and ethical discernment queries. We conclude with a discussion regarding the best practices of ethical discernment and decision-making at the end of life.This study highlights the need to develop more research to better understand the influence and origin of these multidimensional factors determining critical decisions that define the quality of life of patients in a highly sensitive moment. CONCLUSION: We conclude that personal aspects of the physician define their actions more than knowledge or organized structure. It is thus necessary that pediatric oncologists receive ethics and humanistic education.

Asymmetric palatine tonsil in a pediatric patient: Is it always a malignant neoplasm? / Asimetría amigdalina en pediatría: ¿cuándo sospechar malignidad?

Abstract Background: A relatively frequent clinical finding in children is an asymmetric tonsil, which can have multiple etiological possibilities, including a malignant disease. The clinical finding of tonsillar asymmetry is found in approximately 2% of the pediatric population. The incidence of malignancy in the tonsils is low, estimated as 2.5 cases per 10,000 tonsillectomies. Due to its low incidence, the diagnostic tonsillectomy is not justified when tonsillar asymmetry is the only clinical finding. However, it is necessary to identify the critical clinical findings of high suspicion of malignancy that justify the performance of immediate surgery in the pediatric population. Case report: We present the case of a 10-year-old male patient. Four months before admission, the patient started with pharyngodynia and dysphagia, treated as recurrent tonsillitis. Due to exacerbation of the symptoms, orthopnea, and B symptoms, the patient came to consultation; tonsillar asymmetry was observed predominantly on the left side, with exophytic lesions extending to the hypopharynx. We decided to perform an incisional biopsy and tracheostomy due to compromised airway; histopathological diagnosis came back as B-cell lymphoma. Conclusions: Given the clinical scenario of recurrent tonsillitis, unresponsive to conventional medical treatment with antibiotics, tonsillar asymmetry with suspicious tonsillar appearance accompanied by symptoms such as fever, diaphoresis, cervical lymphadenopathy, obstructive symptoms in a pediatric patient, it is necessary to refer the patient to the specialist for timely diagnosis and treatment.

Resumen Introducción: La asimetría amigdalina es un hallazgo clínico relativamente frecuente en los niños. Se ha reportado en el 2% de la población pediátrica e incluye múltiples etiologías, entre ellas enfermedad maligna. La incidencia de malignidad es baja: se estima en 2.5 casos por cada 10,000 amigdalectomías. Por tal motivo, cuando se observa asimetría amigdalina como único hallazgo en la exploración física no se justifica la amigdalectomía con fines diagnósticos. Sin embargo, la incertidumbre de malignidad en el médico y en el paciente obliga a considerar los datos clínicos que permitan sospecharla y justificar la intervención quirúrgica. Caso clínico: Se presenta el caso de un paciente de sexo masculino de 10 años. Inició su padecimiento 4 meses previos a su ingreso hospitalario con faringodinia y disfagia, que fueron diagnosticadas y tratadas como amigdalitis recurrente. Acudió al hospital por agudización de los síntomas, evolucionando con ortopnea y síntomas B. En la exploración física se apreció asimetría amigdalina con aumento de volumen en la amígala izquierda extendida hasta la hipofaringe. Se decidió realizar una biopsia incisional y traqueostomía por compromiso respiratorio. El diagnóstico histopatológico fue linfoma de células B. Conclusiones: Ante un paciente pediátrico con amigdalitis recurrente, que no cede al tratamiento médico convencional y presenta asimetría amigdalina con aspecto sospechoso, acompañada de síntomas como fiebre, diaforesis, adenopatías cervicales y síntomas obstructivos, se deberá referir con el especialista para su diagnóstico y tratamiento oportunos.

Asymmetric palatine tonsil in a pediatric patient: Is it always a malignant neoplasm?

Background: A relatively frequent clinical finding in children is an asymmetric tonsil, which can have multiple etiological possibilities, including a malignant disease. The clinical finding of tonsillar asymmetry is found in approximately 2% of the pediatric population. The incidence of malignancy in the tonsils is low, estimated as 2.5 cases per 10,000 tonsillectomies. Due to its low incidence, the diagnostic tonsillectomy is not justified when tonsillar asymmetry is the only clinical finding. However, it is necessary to identify the critical clinical findings of high suspicion of malignancy that justify the performance of immediate surgery in the pediatric population. Case report: We present the case of a 10-year-old male patient. Four months before admission, the patient started with pharyngodynia and dysphagia, treated as recurrent tonsillitis. Due to exacerbation of the symptoms, orthopnea, and B symptoms, the patient came to consultation; tonsillar asymmetry was observed predominantly on the left side, with exophytic lesions extending to the hypopharynx. We decided to perform an incisional biopsy and tracheostomy due to compromised airway; histopathological diagnosis came back as B-cell lymphoma. Conclusions: Given the clinical scenario of recurrent tonsillitis, unresponsive to conventional medical treatment with antibiotics, tonsillar asymmetry with suspicious tonsillar appearance accompanied by symptoms such as fever, diaphoresis, cervical lymphadenopathy, obstructive symptoms in a pediatric patient, it is necessary to refer the patient to the specialist for timely diagnosis and treatment.

Introducción: La asimetría amigdalina es un hallazgo clínico relativamente frecuente en los niños. Se ha reportado en el 2% de la población pediátrica e incluye múltiples etiologías, entre ellas enfermedad maligna. La incidencia de malignidad es baja: se estima en 2.5 casos por cada 10,000 amigdalectomías. Por tal motivo, cuando se observa asimetría amigdalina como único hallazgo en la exploración física no se justifica la amigdalectomía con fines diagnósticos. Sin embargo, la incertidumbre de malignidad en el médico y en el paciente obliga a considerar los datos clínicos que permitan sospecharla y justificar la intervención quirúrgica. Caso clínico: Se presenta el caso de un paciente de sexo masculino de 10 años. Inició su padecimiento 4 meses previos a su ingreso hospitalario con faringodinia y disfagia, que fueron diagnosticadas y tratadas como amigdalitis recurrente. Acudió al hospital por agudización de los síntomas, evolucionando con ortopnea y síntomas B. En la exploración física se apreció asimetría amigdalina con aumento de volumen en la amígala izquierda extendida hasta la hipofaringe. Se decidió realizar una biopsia incisional y traqueostomía por compromiso respiratorio. El diagnóstico histopatológico fue linfoma de células B. Conclusiones: Ante un paciente pediátrico con amigdalitis recurrente, que no cede al tratamiento médico convencional y presenta asimetría amigdalina con aspecto sospechoso, acompañada de síntomas como fiebre, diaforesis, adenopatías cervicales y síntomas obstructivos, se deberá referir con el especialista para su diagnóstico y tratamiento oportunos.

CRLF2 and IKZF1 abnormalities in Mexican children with acute lymphoblastic leukemia and recurrent gene fusions: exploring surrogate markers of signaling pathways.

The gene fusions BCR-ABL1, TCF3-PBX1, and ETV6-RUNX1 are recurrent in B-cell acute lymphoblastic leukemia (B-ALL) and are found with low frequency in coexistence with CRLF2 (cytokine receptor-like factor 2) rearrangements and overexpression. There is limited information regarding the CRLF2 abnormalities and dominant-negative IKZF1 isoforms associated with surrogate markers of Jak2, ABL, and Ras signaling pathways. To assess this, we evaluated 24 Mexican children with B-ALL positive for recurrent gene fusions at diagnosis. We found CRLF2 rearrangements and/or overexpression, dominant-negative IKZF1 isoforms, and surrogate phosphorylated markers of signaling pathways coexisting with recurrent gene fusions. All the BCR-ABL1 patients expressed CRLF2 and were positive for pCrkl (ABL); most of them were also positive for pStat5 (Jak2/Stat5) and negative for pErk (Ras). TCF3-PBX1 patients with CRLF2 abnormalities were positive for pStat5, most of them were also positive for pCrkl, and two patients were also positive for pErk. One patient with ETV6-RUNX1 and intracellular CRLF2 protein expressed pCrkl. In some cases, the activated signaling pathways were reverted in vitro by specific inhibitors. We further analyzed a TCF3-PBX1 patient at relapse, identifying a clone with the recurrent gene fusion, P2RY8-CRLF2, rearrangement, and phosphorylation of the three surrogate markers that we studied. These results agree with the previous reports regarding resistance to treatment observed in patients with recurrent gene fusions and coexisting CRLF2 gene abnormalities. A marker phosphorylation signature was identified in BCR-ABL1 and TCF3-PBX1 patients. To obtain useful information for the assessment of treatment in B-ALL patients with recurrent gene fusions, we suggest that they should be evaluated at diagnosis for CRLF2 gene abnormalities and dominant-negative IKZF1 isoforms, in addition to the analyses of activation and inhibition of signaling pathways.

Association of Genetic Polymorphisms and Serum Levels of IL-6 and IL-8 with the Prognosis in Children with Neuroblastoma.

There is evidence that high circulating levels of IL-6 and IL-8 are markers of a poor prognosis in various types of cancer, including NB. The participation of these cytokines in the tumor microenvironment has been described to promote progression and metastasis. Our objective was to evaluate the prognostic role of genetic polymorphisms and serum levels of IL-6 and IL-8 in a cohort of Mexican pediatric patients with NB. The detection of the SNPs rs1800795 IL-6 and rs4073 and rs2227306 IL-8 was carried out by PCR-RFLP and the levels of cytokines were determined by the ELISA method. We found elevated circulating levels of IL-8 and IL-6 in NB patients compared to the control group. The genotype frequencies of the rs1800795 IL-6 and rs4073 IL-8 variants were different between the patients with NB and the control group. Likewise, the survival analysis showed that the GG genotypes of rs1800795 IL-6 (p = 0.014) and AA genotypes of rs4073 IL-8 (p = 0.002), as well as high levels of IL-6 (p = 0.009) and IL-8 (p = 0.046), were associated with lower overall survival. We confirmed the impact on an adverse prognosis in a multivariate model. This study suggests that the SNPs rs1800795 IL-6 and rs4073 IL-8 and their serum levels could be promising biomarkers of a poor prognosis, associated with overall survival, metastasis, and a high risk in Mexican children with NB.

Acute myeloid leukemia associated with t(16:21)(p11;q22) in a pediatric patient / Leucemia mieloide aguda asociada con t(16:21)(p11;q22) en un paciente pediátrico

Abstract Background: Rare subgroups of pediatric patients with acute myeloid leukemia (AML), such as t(16:21) (p11;q22), require international cooperation to establish a proper stratification system to assign clinical risk. Case report: Here, we report a 13-year-old female who was admitted for asthenia, fatigue, and intermittent fever. The hematological data showed thrombocytopenia and anemia, and the bone marrow test showed 82.5% blast cells, which were positive for CD13, CD33, CD38, and CD117. Blast cells showed negative myeloperoxidase staining and positive periodic acid-Schiff staining. A diagnosis of AML M6 was made. Cells were positive for the fusion transcript FUS-ERG t(16;21)(p11;q22). The patient achieved morphological remission. However, molecular remission was not achieved, and she died 11 months after diagnosis. Conclusions: It is essential to report this sporadic case of AML to provide clinicians with data for clinical decision-making, such as for risk-group stratification. To the best of our knowledge, this is the first association between this translocation and this morphological subtype.

Resumen Introducción: La leucemia mieloide aguda (LMA) infantil es una enfermedad heterogénea, por lo que existen subgrupos de rara presentación, como aquellos con t(16;21)(p11;q22). Para establecer el riesgo clínico y la estratificación pronóstica adecuada es necesaria la cooperación internacional. Caso clínico: Se reporta el caso de una adolescente de 13 años, admitida por astenia, adinamia y fiebre intermitente. Los datos hematológicos mostraron trombocitopenia y anemia, con un 82.5% de blastos en médula ósea, los cuales fueron positivos para CD13, CD33, CD38 y CD 117. Los blastos fueron negativos para mieloperoxidasa y positivos para ácido peryódico de Schiff. Se realizó el diagnóstico morfológico de LMA M6. Las células fueron positivas para el transcrito FUS-ERG t(16;21)(p11;q22). La paciente alcanzó la remisión morfológica; sin embargo, no fue posible la remisión molecular y falleció 11 meses después del diagnóstico. Conclusiones: Es importante reportar casos en los que se identifique un subtipo muy raro de LMA infantil para incrementar la evidencia clínica y contribuir con elementos que ayuden a tomar decisiones clínicas y lograr la estratificación en grupos de riesgo. Hasta la fecha, este el primer caso reportado en que se asocia el transcrito t(16;21)(p11;q22) con el subtipo morfológico LMA M6.

Acute myeloid leukemia associated with t(16:21)(p11;q22) in a pediatric patient.

Background: Background">Rare subgroups of pediatric patients with acute myeloid leukemia (AML), such as t(16:21) (p11;q22), require international cooperation to establish a proper stratification system to assign clinical risk. Case report: Here, we report a 13-year-old female who was admitted for asthenia, fatigue, and intermittent fever. The hematological data showed thrombocytopenia and anemia, and the bone marrow test showed 82.5% blast cells, which were positive for CD13, CD33, CD38, and CD117. Blast cells showed negative myeloperoxidase staining and positive periodic acid-Schiff staining. A diagnosis of AML M6 was made. Cells were positive for the fusion transcript FUS-ERG t(16;21)(p11;q22). The patient achieved morphological remission. However, molecular remission was not achieved, and she died 11 months after diagnosis. Conclusions: It is essential to report this sporadic case of AML to provide clinicians with data for clinical decision-making, such as for risk-group stratification. To the best of our knowledge, this is the first association between this translocation and this morphological subtype.

Introducción: La leucemia mieloide aguda (LMA) infantil es una enfermedad heterogénea, por lo que existen subgrupos de rara presentación, como aquellos con t(16;21)(p11;q22). Para establecer el riesgo clínico y la estratificación pronóstica adecuada es necesaria la cooperación internacional. Caso clínico: Se reporta el caso de una adolescente de 13 años, admitida por astenia, adinamia y fiebre intermitente. Los datos hematológicos mostraron trombocitopenia y anemia, con un 82.5% de blastos en médula ósea, los cuales fueron positivos para CD13, CD33, CD38 y CD 117. Los blastos fueron negativos para mieloperoxidasa y positivos para ácido peryódico de Schiff. Se realizó el diagnóstico morfológico de LMA M6. Las células fueron positivas para el transcrito FUS-ERG t(16;21)(p11;q22). La paciente alcanzó la remisión morfológica; sin embargo, no fue posible la remisión molecular y falleció 11 meses después del diagnóstico. Conclusiones: Es importante reportar casos en los que se identifique un subtipo muy raro de LMA infantil para incrementar la evidencia clínica y contribuir con elementos que ayuden a tomar decisiones clínicas y lograr la estratificación en grupos de riesgo. Hasta la fecha, este el primer caso reportado en que se asocia el transcrito t(16;21)(p11;q22) con el subtipo morfológico LMA M6.

Efficacy and safety of oral magnesium supplementation in reducing febrile neutropenia episodes in children with solid tumors treated with cisplatin-based chemotherapy: randomized clinical trial.

PURPOSE: Hypomagnesemia has been associated with febrile neutropenia (FN) in pediatric patients receiving cisplatin-based chemotherapy (CDDPBC). The primary aim was to determine whether oral magnesium supplementation reduces FN episodes in pediatric patients with solid tumors treated with CDDPBC. METHOD: This randomized clinical trial, with open-label, single-center, parallel group and superiority design was conducted in Hospital Infantil de Mexico Federico Gomez at Mexico City. Children ≥ 9 years with solid tumors that were to receive a CDDPBC cycle were invited to participate. Each chemotherapy cycle with CDDPBC was randomly assigned to receive oral magnesium supplementation (250 mg/day) or not receive magnesium supplementation (control group). Efficacy was determined by relative risks (RR) with 95% confidence intervals (95% CI) as well as with numbers needed to treat (NNT). Active surveillance was conducted to assess safety in both groups. Analyses were carried out by intention to treat. ClinicalTrials.gov number NCT03449693. RESULTS: One hundred and one chemotherapy cycles with CDDPBC were analyzed (50 in the magnesium supplement arm and 51 in control group). Baseline clinical characteristics were similar comparing both groups. Oral magnesium supplementation reduces FN episodes compared to control group [RR 0.53, (95% CI 0.32-0.89), NNT = 4]. In the supplemented group, patients had fewer episodes of septic shock secondary to FN [RR 0.43, (95% CI 0.02-0.94), NNT = 6] and FN appeared on average 5 days later (p = 0.031). Hypomagnesemia episodes and adverse events were similar across both groups. CONCLUSION: Oral supplementation with magnesium reduces FN episodes neutropenia in pediatric patients with solid tumors treated with CDDPBC.

Survival in pediatric patients with cancer during the COVID-19 pandemic: scoping systematic review.

Background: Coronavirus disease (COVID)-19 has currently affected 8,015,502 million people worldwide with global mortality around 5%. Information in pediatric cancer patients is still limited, but it is emerging day by day. The objective of this scoping review was to analyze the available data associated with COVID-19 infection and mortality in pediatric cancer patients and to provide useful information to plan and design strategies in this group. Methods: A search was conducted, and eight articles were obtained for qualitative analysis; 110 patients were included, all from cross-sectional studies. At the time of publication, all the analyzed documents reported no deaths associated with COVID-19. Results: According to the information, COVID-19 infection appears to be less severe in the pediatric population in comparison with adults and does not appear to be a cause of mortality in patients with childhood cancer. Conclusions: Given the nature of preliminary reports and a short follow-up in cancer patients, it is necessary to have medium- and long-term follow-up studies to determine the effects of infection and modifications to the treatments of these patients.

Introducción: La enfermedad conocida como COVID-19 ha afectado ya a 8,015,502 millones de personas en el mundo, con una mortalidad global de aproximadamente el 5%. La información en pacientes pediátricos con cáncer es aún limitada y está surgiendo día a día. El objetivo de esta revisión sistemática fue conocer los datos disponibles sobre la COVID-19 y la mortalidad en los pacientes pediátricos con cáncer, y aportar información útil para planear y diseñar estrategias en este grupo. Métodos: Se llevó a cabo una búsqueda y se seleccionaron ocho artículos para realizar un análisis cuantitativo; se incluyeron 110 pacientes, todos provenientes de estudios transversales. Al momento de las publicaciones, no se documentaron fallecimientos asociados a la COVID-19 en los documentos analizados. Resultados: De acuerdo con la información de esta revisión sistemática, la COVID-19 parece ser menos grave que en los adultos y no parece ser causa de mortalidad en pacientes pediátricos con cáncer. Conclusiones: Dada la naturaleza de los reportes preliminares y el corto seguimiento en los pacientes con cáncer, es necesario contar con estudios de seguimiento a mediano y largo plazo para conocer los efectos de la infección y de las modificaciones del tratamiento en estos pacientes.

Survival in pediatric patients with cancer during the COVID-19 pandemic: scoping systematic review / Sobrevida en pacientes pediátricos con cáncer durante la pandemia de COVID-19: revisión sistemática exploratoria

Abstract Background: Coronavirus disease (COVID)-19 has currently affected 8,015,502 million people worldwide with global mortality around 5%. Information in pediatric cancer patients is still limited, but it is emerging day by day. The objective of this scoping review was to analyze the available data associated with COVID-19 infection and mortality in pediatric cancer patients and to provide useful information to plan and design strategies in this group. Methods: A search was conducted, and eight articles were obtained for qualitative analysis; 110 patients were included, all from cross-sectional studies. At the time of publication, all the analyzed documents reported no deaths associated with COVID-19. Results: According to the information, COVID-19 infection appears to be less severe in the pediatric population in comparison with adults and does not appear to be a cause of mortality in patients with childhood cancer. Conclusions: Given the nature of preliminary reports and a short follow-up in cancer patients, it is necessary to have medium- and long-term follow-up studies to determine the effects of infection and modifications to the treatments of these patients.

Resumen Introducción: La enfermedad conocida como COVID-19 ha afectado ya a 8,015,502 millones de personas en el mundo, con una mortalidad global de aproximadamente el 5%. La información en pacientes pediátricos con cáncer es aún limitada y está surgiendo día a día. El objetivo de esta revisión sistemática fue conocer los datos disponibles sobre la COVID-19 y la mortalidad en los pacientes pediátricos con cáncer, y aportar información útil para planear y diseñar estrategias en este grupo. Métodos: Se llevó a cabo una búsqueda y se seleccionaron ocho artículos para realizar un análisis cuantitativo; se incluyeron 110 pacientes, todos provenientes de estudios transversales. Al momento de las publicaciones, no se documentaron fallecimientos asociados a la COVID-19 en los documentos analizados. Resultados: De acuerdo con la información de esta revisión sistemática, la COVID-19 parece ser menos grave que en los adultos y no parece ser causa de mortalidad en pacientes pediátricos con cáncer. Conclusiones: Dada la naturaleza de los reportes preliminares y el corto seguimiento en los pacientes con cáncer, es necesario contar con estudios de seguimiento a mediano y largo plazo para conocer los efectos de la infección y de las modificaciones del tratamiento en estos pacientes.

Patient and health service factors associated with delays in cancer treatment for children without social security in Mexico.

BACKGROUND: The objective was to investigate factors associated with patient-related timing (PRT) to seek healthcare and health service-related timing (HSRT) to diagnose cancer and provide treatment to children without social security in Mexico. PROCEDURE: A cross-sectional survey was conducted in 13 Ministry of Health hospitals in the states of Chihuahua, Jalisco, Mexico City, Morelos, Oaxaca, Puebla, Queretaro, State of Mexico, and Tlaxcala. Study participants were parents of recently diagnosed pediatric cancer patients (≤ 17 years of age). Three groups of factors were investigated: (1) patients (child and parent characteristics); (2) healthcare providers (HCPs) (first-contact HCP, institution, perceptions of barriers to healthcare, etc.); and (3) disease factors (cancer type/site, stage/risk at diagnosis). PRT and HSRT-associated factors were identified using multiple negative binomial regressions. RESULTS: The study included 265 children; 49% sought care when symptoms first appeared. The median PRT was seven days, and the median HSRT was 40 days. Parents' perceptions of long wait times for appointments were associated with longer PRT and HSRT. Residing in the lowest or highest socioeconomic regions and persistent or worsening symptoms increased the probability of longer PRT. Older patient age, HCP requests for imaging tests or prescription for steroids, a higher number of doctors consulted, having a urinary tract cancer, and having an advanced stage or high-risk cancer increased the probability of longer HSRT. CONCLUSION: Strategies to shorten lag time from symptom onset to diagnosis and treatment are urgently needed for childhood cancers in Mexico.

The Role of Time as a Prognostic Factor in Pediatric Brain Tumors: a Multivariate Survival Analysis.

There is no evidence that prolonged pre diagnostic symptomatic intervals (PSI) increases the risk of death in pediatric brain tumors. When investigating the role of time previous research had not controlled for confounding variables or measured the pretreatment interval (PTI). We use the term global delay interval (GDI) to describe the sum of PSI and PTI. The aim of this research was to evaluate whether there was a decrease in the probability of survival in children with brain tumors due to a prolonged PSI, PTI and GDI, using a multivariate survival analysis. We retrospective review 127 clinical records labeled with the diagnosis of CNS tumors attended at a specialized pediatric center in Mexico City from January 2008 to December 2012. Patients with PSI and GDI diagnosed between 3 and 6 months showed statistical lower probability of surviving that those with intervals <3 months even when adjusting for age, sex, localization and tumor grade. When stratified for the place of residency and adjusted for sex, age, localization, grade of tumor, type of surgery and coadjuvant therapy, a GDI between 3 and 6 months showed to be a risk factor for the overall survival of brain tumors compared with an interval < 3 months. When analyzing the interaction, high grade tumors are at more risk of dying when GDI was between 3 and 6 months compared to <3 months. Prolonged PSI and GDI showed to be a potential prognostic factor for survival in CNS tumors, especially in high grade tumors. Future prospective research should measure the PSI, PTI and GDI and adjust for covariates in order to properly infer the effect of time in pediatric brain tumors.