RESUMEN
Pentoxifylline is a xanthine that possesses antitumor properties and that can induce higher apoptosis in the leukemic cells of pediatric patients with acute lymphoblastic leukemia (ALL) during treatment with prednisone. We conducted a phase 1 pilot, controlled, randomized trial to evaluate the gene expression modified by pentoxifylline during the steroid window of induction to remission phase in patients newly diagnosed with ALL. Experimental and control treatments induced broad changes in the gene expression profile. Patients who received just prednisone upregulated 377 and downregulated 344 genes, in contrast with patients treated with the experimental treatment (combination of prednisone and pentoxifylline), who demonstrated upregulation of 1319 and downregulation of 1594 genes. The most important genes modified in this pathway are those with proapoptotic activity, the majority of these overexpressed. Thus, the addition of pentoxifylline to the treatment with prednisone during steroid window in patients with ALL modified the gene expression profile and changed different signal pathways of the leukemic cell. The combination of both drugs represents a therapeutic alternative for potentiating antileukemic therapy.
Asunto(s)
Apoptosis/efectos de los fármacos , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Pentoxifilina/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras , Prednisona/administración & dosificación , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Proyectos Piloto , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologíaRESUMEN
BACKGROUND: Acute leukemia is the most common cancer in childhood. Analyzing the spatial distribution of acute leukemia may generate the identification of risk factors. OBJECTIVE: To study the incidence rate of acute leukemia, its geographic distribution, and cluster detection in the metropolitan area of Guadalajara, Mexico. METHODS: We included children under 15 years of age diagnosed with acute leukemia during the period 2010-2014 in the metropolitan area of Guadalajara. Each case was geo-referenced to street level to latitude and longitude coordinates using Quantum Geographic Information System (QGIS). Spatial clusters were found in the location of the acute leukemia cases applying the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm with R statistical software. RESULTS: A total of 269 cases of leukemia were registered, 227 (84%) were acute lymphoblastic leukemia and 42 (16%) acute myeloblastic leukemia. The mean age was 6 ± 4 years. The mean incidence of acute leukemia was 6.44 cases/100,000 inhabitants: El Salto 10.12/100,000, Guadalajara 7.55/100,000, and Tlaquepaque 6.74/100,000. The DBSCAN found three clusters, all located within the municipality of Guadalajara. CONCLUSIONS: The incidence of acute leukemia in our population is higher than that in Canada and the USA. We found three spatial clusters of childhood acute lymphoblastic leukemia in the municipality of Guadalajara, suggesting the presence of local predisposing factors.
Asunto(s)
Leucemia Mieloide Aguda/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Adolescente , Algoritmos , Niño , Preescolar , Análisis por Conglomerados , Femenino , Humanos , Incidencia , Leucemia Mieloide Aguda/etiología , Masculino , México/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , Factores de RiesgoRESUMEN
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.
Asunto(s)
Seguro de Salud , Neoplasias/epidemiología , Vigilancia en Salud Pública , Adolescente , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , México/epidemiología , Neoplasias/diagnóstico , Neoplasias/mortalidad , Prevalencia , Sistema de RegistrosRESUMEN
Introduction: Patients with optic pathway gliomas (OPG) have good survival rates although their long-term quality of life can be affected by the tumor or treatment-related morbidity. This retrospective study sought to describe the clinical presentation and outcomes of children with OPG at a tertiary center in Mexico. Methods: Consecutive patients <18 years-of-age with newly diagnosed OPG between January 2002 and December 2020 at the Hospital Civil de Guadalajara Dr. Juan I. Menchaca in Guadalajara, Mexico were included. Results: Thirty patients were identified with a median age of six years. The most frequent clinical manifestations were loss of visual acuity (40%) and headaches (23%). Neurofibromatosis-1 was found in 23.3% of the patients. Surgery, either biopsy or resection, was done in 20 of 30 patients. Two patients died shortly after initial surgery. The 5-year event-free survival (EFS) was 79.3% ± 10.8% and the 5-year overall survival was 89.5% ± 6.9%. Lower EFS was associated with age less than 3 years, intracranial hypertension at presentation, and diencephalic syndrome. Patients who received surgery as first-line treatment had a 3.1 times greater risk of achieving a performance score of less than 90 points at 6 months after diagnosis (p=0.006). Of 10 patients with vision testing, 5 had improvement in visual acuity, 4 had no changes, and one patient showed worsening. Conclusion: Our data suggests that favorable outcomes can be achieved with OPG in low- and middle-income countries, although a high rate of surgical complications was described leading to a lower overall survival. These data can be used prospectively to optimize treatment at this institute and other middle-income countries through a comprehensive, multidisciplinary approach.
RESUMEN
Patients with acute promyelocytic leukemia (APL) exhibit the t(15;17)(q24.1;q21.2) translocation that produces the promyelocytic leukemia (PML)/retinoic acid receptor α (RARA) fusion gene. Different PML breakpoints yield three alternative molecular transcripts, bcr1, bcr2 and bcr3. The present study reports the simultaneous presence of three PML/RARA transcripts in a pediatric female patient diagnosed with APL, according to the clinical characteristics, immunophenotype and karyotype of the patient. The simultaneous presence of the PML/RARA transcripts were detected using reverse transcription-quantitative PCR (RT-qPCR). This was confirmed with HemaVision-28N Multiplex RT-qPCR, HemaVision-28Q qualitative RT-qPCR and the AmpliSeq RNA Myeloid Panel. To the best of our knowledge, the pediatric patient described in the present study is the first case found to exhibit all three PML/RARA transcripts (bcr1, bcr2 and bcr3). Additionally, a microarray analysis was performed to determine the expression profile, potential predictive biomarkers and the implications of this uncommon finding. According to the information obtained from molecular monitoring, the results reported in the present study were associated with a good patient prognosis. In addition, upregulated genes that are rare in acute myeloid leukemia were identified, and these genes may be promising diagnostic biomarkers for further study. For example, CCL-1 is present in leukemic stem cells, causing treatment failure and relapse, and α- and ß-defensins have been reported exclusively in chronic myeloid leukemia. However, the results of the present study confirmed that they may also be present in APL. Thus, these findings suggested a possible signaling pathway that involves the PML/RARA oncoprotein in APL.
RESUMEN
Prior to 2005, 51% of children in Mexico diagnosed with cancer received no standardized optimal multidisciplinary medical care. A government-subsidized national cancer treatment program was therefore created for these patients and a National Cooperative Childhood Cancer Treatment Group was consequently formed for these patients. Pediatric patients with a proven diagnosis of leukemia, lymphoma or solid tumor and who were registered in the Popular Medical Insurance (PMI) program from January 2007 to December 2010, are described in this report. These patients had been enrolled and registered in one of the 49 nationwide certified medical institutions in Mexico. The national incidence and frequency data for childhood cancers were analyzed for the whole program. At the end of a 4-year study, the analysis revealed that 8,936 children from across Mexico had been diagnosed with cancer. The incidence rate for the PMI patients was 150.3/million/year (2010) for children of 0-18 years. The highest age incidence rate was 51.9 between 0 and 4 years and boys were the predominant group for all types of cancer. The leukemia incidence was 75.3/million/year (2010), and an average frequency of 50.75% throughout the 4 years. The overall mortality rate was measured at 5.4/100,000/year (2010). This study demonstrates a high frequency and incidence of childhood cancer and a beneficial impact of the PMI program over the quality of life in these children.
Asunto(s)
Seguro de Salud , Americanos Mexicanos/estadística & datos numéricos , Neoplasias/epidemiología , Salud Pública , Adolescente , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , México/epidemiología , Neoplasias/diagnóstico , Neoplasias/mortalidad , Pronóstico , Desarrollo de Programa , Sistema de Registros , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Objectives: To determine whether air pollution or changes in SARS-CoV-2 lineages lead to an increase in mortality. Methods: Descriptive statistics were used to calculate rates of infection (2020-2021). RT-PCR was used to compare viral loads from October 2020 to February 2021. Next-generation sequencing (NGS) (n = 92) was used to examine and phylogenetically map SARS-CoV-2 lineages. A correlative "air pollution/temperature" index (I) was developed using regression analysis. PM2.5, PM10, O3, NO2, SO2, and CO concentrations were analyzed and compared to the mortality. Results: The mortality rate during the last year was â¼32%. Relative SARS-CoV-2 viral loads increased in December 2020 and January 2021. NGS revealed that approximately 80% of SARS-CoV-2 linages were B.1.243 (33.7%), B1.1.222 (11.2%), B.1.1 (9%), B.1 (7%), B.1.1.159 (7%), and B.1.2 (7%). Two periods were analyzed, the prehigh- and high-mortality periods and no significant lineage differences or new lineages were found. Positive correlations of air pollution/temperature index values with mortality were found for IPM2.5 and IPM10. INO2. ISO2, and ICO but not for O3. Using ICO, we developed a model to predict mortality with an estimated variation of â¼±5 deaths per day. Conclusion: The mortality rate in the MZG was highly correlated with air pollution indices and not with SARS-CoV-2 lineage.
RESUMEN
Infant acute lymphoblastic leukemia (ALL) represents poor prognosis despite intensive chemotherapy. Rearrangements of chromosome 11q23 are not observed in 34% of the cases. Infant ALL patients with t(5;15)(p15;q11-13) are rare and sporadic. In large series of infant ALL studies, 6 patients have been reported. We present a new case of an infant ALL patient with t(5;15)(p15;q11-13), and a literature review. Considering the data provided by our case and previous reports, we reinforce that this chromosomal abnormality is characteristic of ALL patients under 12 months of age sharing break point in 5p15 and 15q11-13 and strengthen the existence of an infant ALL subgroup characterized by pre-B L1 ALL, CD10-positive, complete remission (100%), and event-free survival (71%), with a relatively good prognosis and clearly less severe than the 11q23 rearrangement cases. This abnormality can be considered a recurrent abnormality on this nosologic group.
Asunto(s)
Cromosomas Humanos Par 15 , Cromosomas Humanos Par 5 , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocación Genética , Femenino , Humanos , Lactante , Neprilisina/análisis , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , PronósticoRESUMEN
Sweet syndrome (SS) is an acute febrile neutrophilic dermatosis that is histologically characterized by an infiltration of the dermis by neutrophils. A 12-year-old adolescent female patient recently diagnosed with acute promyelocytic leukemia presented with fever and was hospitalized for antibiotic management after 22 days of being treated with a treatment protocol based on daunorubicin, all-trans retinoic acid (ATRA), and prophylaxis with dexamethasone, the patient developed erythematous skin lesions located mostly on the extremities. Lesions evolved into painful subcutaneous nodules, and one lesion evolved into a 2.5-cm blister with a purple and necrotic base. A skin biopsy was performed and showed neutrophilic dermatosis which confirmed the diagnosis of SS. The patient's clinical features complied with criteria for differentiation syndrome complicated by shock. Two days after ATRA was suspended, the patient presented resolution of the fever and skin lesions. SS is a rare neutrophilic dermatosis secondary to an innate immune disorder classified into four categories: classical (idiopathic), para-inflammatory, paraneoplastic or pregnancy-related. SS has been described in patients with acute myeloid leukemia in adults secondary to the use of drugs such as ATRA or as a part of a paraneoplastic syndrome. SS can occur exceptionally in children with myeloid leukemia secondary to the use of drugs such as ATRA.
RESUMEN
BACKGROUND: Severe ischemia-reperfusion injury (SIRI) seems to be the key factor that can significantly affect the function of both native kidneys and renal allografts. Therefore, the development of a successful strategy is of a paramount importance in both basic and clinical research. METHODS: To determine the effects of SIRI on the native kidney function, a murine model was planned as follows: group 1 (n = 6) mice underwent to nephrectomy plus ischemia-reperfusion injury for 30 minutes; group 2 (n = 6) mice underwent to nephrectomy without ischemia-reperfusion injury and thus served as sham controls for SIRI. The results of serum creatinine (SCr) were analyzed using Mann-Whitney U tests to calculate the significance between mean values. Survival between groups was measured by Kaplan-Meier test. RESULTS: To reliably achieve an elevation of SCr levels animals were exposed to a SIRI. The values of SCr increased from 0.35 (SD, 0.09) mg/dL to about 2-fold within 2 days and 3-fold within the following 5 days. Under these given conditions the mice displayed signs and histologic findings of severe kidney damage. The survival rate was about 83% of the animals within a week, and they showed no capacity of complete spontaneous self-regeneration. CONCLUSIONS: In this study, we aim to establish a murine model with extensive structural kidney damage and significant elevation of SCr levels, which could be used in basic and translational research of transplantation and regenerative therapies.
Asunto(s)
Modelos Animales de Enfermedad , Trasplante de Riñón , Insuficiencia Renal/etiología , Daño por Reperfusión/complicaciones , Animales , Creatinina/sangre , Riñón/fisiopatología , Masculino , Ratones , Ratones Endogámicos BALB C , Insuficiencia Renal/patología , Insuficiencia Renal/fisiopatología , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatologíaRESUMEN
BACKGROUND: Procalcitonin and C-reactive-protein are inflammatory markers for sepsis. The authors evaluated their sensitivity and specificity in pediatric patients with cancer and febrile neutropenia. PROCEDURE: Serum procalcitonin and C-reactive-protein were evaluated. Patients (n = 54) were divided into 2 groups, with severe infection (n = 18) or without documented infection (n = 36). RESULTS: Procalcitonin and C-reactive protein were significantly higher in the high-risk group. Procalcitonin displayed 72.2% sensitivity and 80.5% specificity. C-reactive-protein had a sensitivity of 77.7% and specificity of 77.2%. CONCLUSIONS: Procalcitonin is an accurate predictor of bacterial infection in neutropenic children, while C-reactive-protein may be a better screening test in emergency settings.
Asunto(s)
Infecciones Bacterianas/sangre , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Calcitonina/sangre , Neoplasias/sangre , Neutropenia/sangre , Precursores de Proteínas/sangre , Adolescente , Bacterias/patogenicidad , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Péptido Relacionado con Gen de Calcitonina , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , México/epidemiología , Neoplasias/epidemiología , Neoplasias/microbiología , Neutropenia/epidemiología , Neutropenia/microbiología , Pronóstico , Estudios Prospectivos , Curva ROC , Sensibilidad y EspecificidadRESUMEN
Background: Meeting the nutritional needs of pediatric patients on oncology services in low budget public hospitals of Mexico is a continuous challenge, due to its financial resources. Objective: To evaluate the effectiveness of a nutritional strategy for children and adolescents with cancer in a public hospital of Mexico, based on a complacency diet. Methods: Across-sectional study included 58 children and adolescents (1-18 years old). An assessment of nutritional status was applied and a dietary diary was elaborated for 24 hours with the double weight method. Results: 43 patients (74.4%) had an adequate nutritional status. The average energy intake was 72.8% and average protein intake 168.3% of the requirements. The hospital meals accounted for 67.5% of the energy intake, 28.5% resulted from snacks and 3.9% from oral nutritional supplements or polymeric smoothies. Conclusion: The nutritional strategy based on offering a menu at the request supported by smoothies or oral nutritional supplements and the permission to introduce snacks to the hospital offers convenience and flexibility for meal times and favors the energy intake in hospitalized pediatric oncology patients.
Introducción: debido a la escasez de recursos económicos, los hospitales públicos de México tienen un reto continuo para satisfacer las necesidades nutricionales de niños en los servicios de oncología pediátrica. Objetivo: evaluar la eficacia de una estrategia nutricional en niños y adolescentes con cáncer, de un hospital público de México, basada en una dieta a complacencia. Métodos: se llevó a cabo un estudio transversal en el que se incluyeron 58 niños y adolescentes (1-18 años de edad). Se realizó una evaluación antropométrica del estado nutricio y se elaboró un diario dietético durante 24 horas con el método de doble pesada. Resultados: 43 pacientes (74.4%) tenían un estado nutricio adecuado. El consumo promedio de energía fue 72.8% y de proteínas 168.3% del requerimiento. Del total de las calorías consumidas 67.5% provenían del menú hospitalario, 28.5% de refrigerios y 3.9% de suplementos alimenticios o licuados artesanales. Conclusión: la estrategia nutricional basada en una dieta a complacencia apoyada por licuados y suplementos alimenticios más un permiso para la introducción de refrigerios al hospital, favoreció la ingestión calórica, ofreció comodidad y flexibilidad durante las horas de comida a los pacientes oncológicos pediátricos hospitalizados.
Asunto(s)
Ingestión de Energía , Desnutrición/dietoterapia , Neoplasias/complicaciones , Estado Nutricional , Apoyo Nutricional/métodos , Adolescente , Factores de Edad , Niño , Preescolar , Estudios Transversales , Registros de Dieta , Suplementos Dietéticos , Femenino , Servicio de Alimentación en Hospital/organización & administración , Hospitales Públicos , Humanos , Lactante , Masculino , Desnutrición/etiología , MéxicoRESUMEN
BACKGROUND: The subjective global assessment (SGA) is a simple, sensitive tool used to identify nutritional risk. It is widely used in the adult population, but there is little evidence on its effectiveness in children with cancer. OBJECTIVE: This cross-sectional study was undertaken to demonstrate significant correlation between a simplified version of the Patient-Generated SGA (PG-SGA) and anthropometric assessment to identify nutritional status in children recently diagnosed with cancer. METHODS: The nutritional status of 70 pediatric cancer patients was assessed with the PG-SGA and anthropometric measurements. The relation between the assessments was tested with ANOVA, independent samples t-test, Kappa statistic, and non-parametric Spearman and Kendall correlation coefficient. The PG-SGA divided the patients into four groups: well nourished, mildly, moderately and severely malnourished. RESULTS: The prevalence of malnutrition according to the PG-SGA was 21.4%. The correlations (r ≥ 0.300, p < 0.001) and the concordance (k ≥ 0.327, p < 0.001) between the PG-SGA and anthropometric indicators were moderate and significant. CONCLUSIONS: The results indicate that the PG-SGA is a valid tool for assessing nutritional status in hospitalized children recently diagnosed with cancer. It is important to emphasize that the subjective assessment does not detect growth retardation, overweight or obesity.
Asunto(s)
Neoplasias/fisiopatología , Evaluación Nutricional , Estado Nutricional , Adolescente , Antropometría , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Desnutrición/diagnóstico , Desnutrición/fisiopatologíaRESUMEN
Acute lymphoblastic leukemia (ALL) accounts for 30% of all pediatric cancers. Currently available treatments exhibit toxicity and certain patients may develop resistance. Thus, less toxic and chemoresistance-reversal agents are required. In the present study, the potential effect of curcumin, a component of Curcuma longa, as a pharmacological co-adjuvant of several chemotherapeutic agents against ALL, including prednisone, 6-mercaptopurine, dexamethasone, cyclophosphamide, l-asparaginase, vincristine, daunorubicin, doxorubicin, methotrexate and cytarabine, was investigated in the REH ALL cell line cultures treated in combination with chemotherapeutic agents and curcumin. The results of cell viability, gene expression and activation of NF-κB and caspase 3 indicated that curcumin potentiates the anticancer effects of the aforementioned chemotherapeutic agents in the REH ALL cell line. Following treatment with the above chemotherapeutic agents, curcumin enhanced caspase-3 activation and downregulated nuclear factor-kappa B (NF-κB) activation. Curcumin also downregulated the oxidative stress induced by certain chemotherapies. Notably, curcumin did not affect the gene expression of cell survival proteins such as B-cell lymphoma (Bcl)-2, Bcl-extra large, survivin, c-Myc and cyclin D1, which are regulated by the NF-κB transcription factor. In conclusion, curcumin has the potential to improve the effect of chemotherapeutic agents against ALL.
RESUMEN
Here we present a male patient with acute myeloid leukemia (AML) initially diagnosed as M5 and with karyotype 46,XY. After induction therapy, he underwent a HLA-matched allogeneic hematopoietic stem cell transplantation, and six years later he relapsed as AML M1 with an abnormal karyotype //47,XX,+10[2]/47,XX,+11[3]/48,XX,+10,+11[2]/46,XX[13]. Based on this, we tested the possibility of donor cell origin by FISH and molecular STR analysis. We found no evidence of Y chromosome presence by FISH and STR analysis consistent with the success of the allogeneic hematopoietic stem cell transplantation from the female donor. FISH studies confirmed trisomies and no evidence of MLL translocation either p53 or ATM deletion. Additionally 28 fusion common leukemia transcripts were evaluated by multiplex reverse transcriptase-polymerase chain reaction assay and were not rearranged. STR analysis showed a complete donor chimerism. Thus, donor cell leukemia (DCL) was concluded, being essential the use of cytological and molecular approaches. Pediatric DCL is uncommon, our patient seems to be the sixth case and additionally it presented a late donor cell leukemia appearance. Different extrinsic and intrinsic mechanisms have been considered to explain this uncommon finding as well as the implications to the patient.
RESUMEN
We analysed the results of three protocols from 1990 to 2005. Protocol I (1990-1996) consisted of a 2 year VAPA regime. Protocol II (1996-2003) on 1 year daunorubicin/cytarabine alternating with etoposide/cytarabine. Protocol III (2003-2005) on six cycles MRC AML 10 modified. Patients with de novo acute myeloid leukemia 0 to 18 years were included. Demographic and clinical characteristics were analysed. Patients with >100,000 leukocytes, M4 or M5 and primary CNS disease were considered high risk. We compared remission rate, overall and event-free survival. Descriptive statistics, chi square, Kaplan-Meier and long rank tests were used. One hundred forty-five patients were included, 46 in Protocol I; 60 in II and 39 in III. There were no differences in characteristics between groups, except for more low risk patients in Protocol II (61%vs. 43% and 41%. (p = 0.05). Remission rate for Protocol I was 52%, for II 50% and for III 92% (p = 0.0001). Relapse was 18, 30 and 35, respectively (p = 0.141). Five-year event-free survival was 17.9% +/- 6.6%, 15.5% +/- 4.1% and 43.5% +/- 4.1% (s.e) (p = 0.0002). Five-year overall survival was 19.5% +/- 8%, 17.2% +/- 5.9% and 51.2% +/- 4.1% (s.e) (p = 0.0002). The results were superior in the MRC-10 derived protocol.