RESUMO
Few studies identifying genomic aspects in pediatric acute myeloid leukemia patients in Latin American countries have been reported. The aim of this study was to identify genomic alterations, clinical characteristics and outcomes in a cohort of pediatric AML patients. This descriptive observational cohort study included patients with confirmed de novo acute myeloid leukemia up to 18 years of age. Cytogenetics and conventional FISH analysis, next-generation sequencing and PCR testing were performed. The correlation of genomic data with treatment response and outcomes were analyzed. Of the 51 patients analyzed, 67.4% had a cytogenetic abnormality and 74.5% had a genetic variant. FLT3 variants (ITD or TKD D835) were found in 27.4%, followed by NRAS (21.6%), KRAS (13.7%) and WT1 and KIT (11.8%). Patients were stratified by risk (66.6% high-risk) after the end of induction. FLT3-ITD was associated with relapse (OR 11.25; CI 1.89-66.72, p 0.006) and NRAS with death during induction (OR 16.71; CI 1.51-184.59, p 0.022). Our study highlights the importance of rapid incorporation of genetic testing in pediatric AML in Colombia, as it directly affects treatment decisions and outcomes. Incorporation of targeted therapies with conventional chemotherapy is an increasingly urgent need in pediatric patients.
Assuntos
Leucemia Mieloide Aguda , Humanos , Colômbia/epidemiologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Aberrações Cromossômicas , Recidiva , Genômica , Mutação , Prognóstico , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
BACKGROUND AND AIM: Different studies have shown pharmacogenetic variants related to drug toxicity in acute myeloid leukemia (AML) patients. Our aim was to identify the association between ABCB1, CDA, DCK, GSTT1, and GSTM1 variants with clinical outcomes and toxicity in pediatric patients with AML. METHODS: Fifty-one confirmed de novo AML pediatric patients were included. A SNaPshot™ assay and conventional PCR were used to evaluate ABCB1, CDA, DCK, GSTT1, and GSTM1 variants. Clinical outcomes and toxicity associations were evaluated using odds ratios and Chi-square analysis. RESULTS: Patients carrying ABCB1 (1236C > T, rs1128503) GG genotype in had a 6.8 OR (CI 95% 1.08-42.73, p = .044) for cardiotoxicity as compared to patients carrying either AA or GA genotypes 0.14 OR (CI 95% 0.023-0.92, p = .044). For ABCB1 (1236G > A rs1128503/2677C > A/T rs2032582/3435G > A rs1045642) AA/AA/AA combined genotypes had a strong association with death after HSTC OR 13.73 (CI 95% 1.94-97.17, p = .009). Combined genotypes GG/CC/GG with CDA (79A > C, rs2072671) CA genotype or CDA (-451G > A, rs532545) CT genotype, had a 4.11 OR (CI 95% 2.32-725, p = .007) and 3.8 OR (CI 95% 2.23-6.47, p = .027) with MRD >0.1% after first chemotherapy cycle, respectively. CONCLUSION: Our results highlight the importance of pharmacogenetic analysis in pediatric AML, particularly in populations with a high degree of admixture, and might be useful as a future tool for patient stratification for treatment.
Assuntos
Leucemia Mieloide Aguda , Farmacogenética , Humanos , Criança , Colômbia/epidemiologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Genótipo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/uso terapêuticoRESUMO
BACKGROUND: Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a subtype of pediatric leukemia with high risk factors and poor outcome. There are few reports of its prevalence in Latin America. AIM: This study evaluated the frequency and clinical and biological characteristics of Ph-like ALL in a pediatric cancer center in Colombia. METHODS: The Ph-like genetic profile was analyzed by a low-density array (LDA). Samples from patients with Ph-like ALL were analyzed by fluorescent in situ hybridization for cytokine receptor like factor 2 (CRLF2) and ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL1) rearrangements. Copy number variations were assessed by multiplex ligation probe amplification. RESULTS: Data from 121 patients were analyzed. Fifteen patients (12.4%) had Ph-like ALL, and these patients had significantly higher leukocyte counts at diagnosis and higher levels of minimal residual disease on days 15 and 33 of induction than patients without the Ph-like subtype. There were no significant differences in sex, age, or response to prednisone at day 8 between the two groups. CRLF2 rearrangements were identified in eight patients, and ABL1 rearrangements were identified in two patients. Other genetic alterations alone or in combination were identified in 77% of patients, including deletions in cyclin dependent kinase inhibitor 2 A/B (46.2%), IKAROS family zinc finger 1 (38.3%), and paired box 5 (30.8%). CONCLUSIONS: Ph-like ALL had a 12.4% prevalence in our cohort of patients with pediatric ALL. The identification of this group of patients has importance for risk stratification and future targeted therapy.
Assuntos
Fator de Transcrição Ikaros , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Colômbia/epidemiologia , Variações do Número de Cópias de DNA , Humanos , Fator de Transcrição Ikaros/genética , Hibridização in Situ Fluorescente , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Encaminhamento e ConsultaRESUMO
Objetivo:Determinar la eficacia del tratamiento combinado de sales de rehidratación oral (SRO) y racecadotrilo frente al uso de SRO y placebo en los niños de 3 a 36 meses con enfermedad diarreica aguda (EDA), en el Servicio de Emergencia del Hospital Vicente Corral Moscoso (HVCM). Método:Ensayo clínico controlado ciego, en niños de 3 a 36 meses del servicio de emergencia del HVCM, con cuadro de enfermedad diarreica aguda, sin deshidratación o con deshidratación leve o moderada, que no necesiten hos-pitalización, sin tratamiento antidiarreico o antibiótico previo, cuyos padres o representantes legales firmen el consentimiento informado. Se reclutaron 79 pacientes, 45 en el grupo SRO más racecadotrilo y 34 grupo SRO más placebo. Resultados:Los grupos fueron comparables clínicamente, los pacientes del grupo SRO más racecadotrilo mostraron una diferencia significativa en el número de diarreas por día a partir de las 48 horas [2.7 (DS: ±1.5), grupo SRO más pla-cebo 4.1 (DS: ±2,6)] con una p: 0.012; a las 72 horas, el grupo racecadotrilo [2.2 (DS: ±1.7), y grupo placebo 3.3 (DS: ±2,5)] con p: 0.027. No se encontró diferencia significativa en las primeras 24 horas (p: 0.27). Conclusiones:Racecadotrilo es un medicamento eficaz en disminuir el número de diar-reas a partir de las 48 horas, en el tratamiento inicial de niños con EDA, acompañando a la terapia con SRO en un grupo de pacientes atendidos en el Hospital Vicente Corral Moscoso.
Objective:To determine the efficacy of the combined treatment of oral rehydration salts (ORS) and racecadotril against the use of ORS and placebo in children aged between 3 and 36 months with acute diarrhea disease (ADD), in the Vicente Corral Moscoso Hospital (VCMH) emergency service. Method:It is a blind controlled clinical trial in children from 3 to 36 months of the VCMH emergency service, with acute diarrheic disease, without dehydration or mild or moderate dehydration; they do not need hospitalization, without previous antidiarrheal treatment or antibiotic, if their parents or legal representatives sign the informed consent. A total of 79 patients were recruited, 45 in the ORS plus racecadotril group and 34 ORS plus placebo group. Results:The groups were clinically comparable, the patients in the ORS plus racecadotril group showed a significant difference in the number of diarrheas per day from 48 hours [2.7 (DS: ± 1.5), the ORS plus placebo group 4.1 (DS: ± 2.6)] with a p: 0.012; at 72 hours, the racecadotril group [2.2 (DS: ± 1.7), and placebo group [3.3 (DS: ± 2.5)] with p: 0.027. No significant difference was found in the first 24 hours (p: 0.27). Conclusions:Racecadotril is an effective medication to reduce the number of diarrhea after 48 hours, in the initial treatment of children with ADD accompanying ORS therapy in a group of patients treated at the Vicente Corral Moscoso Hospital.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Resultado do Tratamento , Disenteria , Assistência Ambulatorial , Pediatria , Desidratação , GastroenteriteRESUMO
Motivados por la alta incidencia y mortalidad del cáncer gástrico en el Ecuador, patología que se constituye en la principal causa de muerte de los ecuatorianos dentro de todos los tumores, especialmente en la Provincia de Manabí, que en esta última década se ha constituido en un grave problema de centros de diagnósticos. Después de haber constatado en 1987 que el 19,3xciento de los cánceres procedían de un área rural ubicada en la zona central de la provincia, iniciamos nuestro primer trabajo de despistaje poblacional en la parroquia Alajuela y posteriormente en San Plácido y Calderón. La encuesta epidemiológica detreminó el consumo de manera importante de alimentos orgánicos de origen animal (carne y/o pescado), conservados en sal en un 75,5xciento de la población y, el análisis de la concentración de nitritos en 30 pozos que reportó 2 con elevada concentración y 8 con un ligero aumento...
Assuntos
Humanos , Zona Rural , Neoplasias Gástricas/epidemiologia , Equador , PacientesRESUMO
Existe un incremento de las afecciones gástricas en nuestro país, especialmente de la úlcera y el cáncer gástrico, constituyéndose este último como la primera causa de mortalidad dentro de todos los tumores, por motivo de su diagnóstico tardío. Nosotros reportamos un caso de cáncer gástrico incipiente-diminuto, con seguimiento clínico y endoscópico de 3 años y medio con intervalos asintomáticos y constatación macroscópica de cicatrizzación y reactivación después del tratamiento médico, compatible con la historia natural que puede presentar en su evolución el cáncer gástrico, de acuerdo a trabajos publicados por autores japoneses. La presencia de helicobacter pylori fue evidenciada al inicio del estudio por test de ureasa y anatomía patológica. El diagnóstico endoscópico fue el de un cáncer gástrico diminuto (8mm. de diámetro), de tipo IIa+IIc con estudio histológico de adenocarcinoma diferenciado de tipo tubular intramucuso asociado a gastritis crónica atrófica y metaplasia intestinal...