RESUMEN
The study analyzes the current status of personalized medicine in pediatric oncology in Spain. It gathers national data on the tumor molecular studies and genomic sequencing carried out at diagnosis and at relapse, the centers that perform these studies, the technology used and the interpretation and clinical applicability of the results. Current challenges and future directions to achieve a coordinated national personalized medicine strategy in pediatric oncology are also discussed. Next generation sequencing-based (NGS) gene panels are the technology used in the majority of centers and financial limitations are the main reason for not incorporating these studies into routine care. Nowadays, the application of precision medicine in pediatric oncology is a reality in a great number of Spanish centers. However, its implementation is uneven and lacks standardization of protocols; therefore, national coordination to overcome the inequalities is required. Collaborative work within the Personalized Medicine Group of SEHOP is an adequate framework for encouraging a step forward in the effort to move precision medicine into the national healthcare system.
Asunto(s)
Hematología , Neoplasias , Niño , Consenso , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Neoplasias/genética , Neoplasias/patología , Neoplasias/terapia , Medicina de Precisión/métodos , EspañaRESUMEN
INTRODUCTION: Cancer and blood disorders in children are rare. The progressive improvement in survival over the last decades largely relies on the development of international academic clinical trials that gather the sufficient number of patients globally to elaborate solid conclusions and drive changes in clinical practice. The participation of Spain into large international academic trials has traditionally lagged behind of other European countries, mainly due to the burden of administrative tasks to open new studies, lack of financial support and limited research infrastructure in our hospitals. METHODS: The objective of ECLIM-SEHOP platform (Ensayos Clínicos Internacionales Multicéntricos-SEHOP) is to overcome these difficulties and position Spain among the European countries leading the advances in cancer and blood disorders, facilitate the access of our patients to novel diagnostic and therapeutic approaches and, most importantly, continue to improve survival and reducing long-term sequelae. ECLIM-SEHOP provides to the Spanish clinical investigators with the necessary infrastructural support to open and implement academic clinical trials and registries. RESULTS: In less than 3 years from its inception, the platform has provided support to 20 clinical trials and 8 observational studies, including 8 trials and 4 observational studies where the platform performs all trial-related tasks (integral support: trial setup, monitoring, etc.) with more than 150 patients recruited since 2017 to these studies. In this manuscript, we provide baseline metrics for academic clinical trial performance that permit future comparisons. CONCLUSIONS: ECLIM-SEHOP facilitates Spanish children and adolescents diagnosed with cancer and blood disorders to access state-of-the-art diagnostic and therapeutic strategies.
Asunto(s)
Ensayos Clínicos como Asunto/estadística & datos numéricos , Cooperación Internacional , Estudios Multicéntricos como Asunto/estadística & datos numéricos , Estudios Observacionales como Asunto/estadística & datos numéricos , Objetivos Organizacionales , Sociedades Médicas/organización & administración , Adolescente , Supervivientes de Cáncer , Niño , Neoplasias Hematológicas/terapia , Hematología/organización & administración , Humanos , Oncología Médica/organización & administración , Neoplasias/terapia , Pediatría/organización & administración , EspañaRESUMEN
Purpose: Despite numerous advances, survival remains dismal for children and adolescents with poor prognosis cancers or those who relapse or are refractory to first line treatment. There is, therefore, a major unmet need for new drugs. Recent advances in the knowledge of molecular tumor biology open the door to more adapted therapies according to individual alterations. Promising results in the adult anticancer drug development have not yet been translated into clinical practice. We report the activity in early pediatric oncology trials in Spain. Methods: All members of the Spanish Society of Pediatric Hematology Oncology (SEHOP) were contacted to obtain information about early trials open in each center. Results: 22 phase I and II trials were open as of May 2015: 15 for solid tumors (68 %) and 7 for hematological malignancies (32 %). Fourteen (64 %) were industry sponsored. Since 2010, four centers have joined the Innovative Therapies For Children With Cancer, an international consortium whose aim is developing novel therapies for pediatric cancers. A substantial number of studies have opened in these 5 years, improving the portfolio of trials for children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents and their benefits. Conclusions: Clinical trials are the way to evaluate new drugs, avoiding the use of off-label drugs that carry significant risks. The Spanish pediatric oncology community through the SEHOP is committed to develop and participate in collaborative academic trials, to favor the advancement and optimization of existing therapies in pediatric cancer (AU)
No disponible
Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Oncología Médica/métodos , Neoplasias/epidemiología , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/prevención & control , España/epidemiología , Sociedades Médicas/organización & administración , Sociedades Médicas/normas , Pediatría/métodos , Terminación Anticipada de los Ensayos Clínicos/métodosRESUMEN
PURPOSE: Despite numerous advances, survival remains dismal for children and adolescents with poor prognosis cancers or those who relapse or are refractory to first line treatment. There is, therefore, a major unmet need for new drugs. Recent advances in the knowledge of molecular tumor biology open the door to more adapted therapies according to individual alterations. Promising results in the adult anticancer drug development have not yet been translated into clinical practice. We report the activity in early pediatric oncology trials in Spain. METHODS: All members of the Spanish Society of Pediatric Hematology Oncology (SEHOP) were contacted to obtain information about early trials open in each center. RESULTS: 22 phase I and II trials were open as of May 2015: 15 for solid tumors (68 %) and 7 for hematological malignancies (32 %). Fourteen (64 %) were industry sponsored. Since 2010, four centers have joined the Innovative Therapies For Children With Cancer, an international consortium whose aim is developing novel therapies for pediatric cancers. A substantial number of studies have opened in these 5 years, improving the portfolio of trials for children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents and their benefits. CONCLUSIONS: Clinical trials are the way to evaluate new drugs, avoiding the use of off-label drugs that carry significant risks. The Spanish pediatric oncology community through the SEHOP is committed to develop and participate in collaborative academic trials, to favor the advancement and optimization of existing therapies in pediatric cancer.
Asunto(s)
Ensayos Clínicos como Asunto , Oncología Médica/tendencias , Neoplasias/terapia , Pediatría/tendencias , Adolescente , Niño , Femenino , Humanos , Masculino , Oncología Médica/métodos , Pediatría/métodos , EspañaRESUMEN
No disponible
Asunto(s)
Humanos , Niño , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Salud Infantil/historia , Leucemia/clasificación , Leucemia/complicaciones , Neoplasias/inducido químicamente , Neoplasias/metabolismo , Neoplasias/complicaciones , Salud Infantil/legislación & jurisprudencia , Leucemia/prevención & control , Neoplasias/economíaRESUMEN
The main objectives of this study were to describe the characteristics of children with influenza infection during the postpandemic outbreak, and to compare sociodemographic and clinical data between patients who required hospitalization and those managed on an outpatient basis with a matched case-control study design. This is a multicentre paediatric study in Spain that included patients aged 6 month to 18 years in whom influenza infection was confirmed by real-time reverse transcription-polymerase chain reaction between December 2010 and March 2011. Among the 143 admitted patients, the main reason for admission was respiratory failure (123/143). In 55 there was some previously known disease. The median age was lower in patients without comorbidity (1.8 years: interquartile range 1.0-3.0 versus 5.3 years: interquartile range 1.3-10.7); p <0.01). The lag time from onset of symptoms to starting antiviral treatment was correlated with the length of hospital stay (Rho Spearman = + 0.32; p 0.01). Twenty patients required admission to the paediatric intensive care units, all due to respiratory failure. Children with chest X-ray opacities in more than one quadrant more frequently required admission to intensive care. Having a neurological disease conferred the highest risk of requiring hospitalization (OR 17.18) in a multivariate analysis. This study concludes that influenza in the paediatric population requiring hospitalization during the postpandemic season affected mainly children with neurological or pulmonary comorbidities and children of parents with a lower educational level. Most of the influenza infections caused respiratory symptoms, although neurological manifestations were also observed. Early initiation of oseltamivir was associated with a shorter length of hospital stay.
Asunto(s)
Hospitalización/estadística & datos numéricos , Gripe Humana/patología , Niño , Preescolar , Comorbilidad , Femenino , Humanos , Lactante , Gripe Humana/epidemiología , Enfermedades Pulmonares/complicaciones , Masculino , Enfermedades del Sistema Nervioso/complicaciones , Orthomyxoviridae/genética , Orthomyxoviridae/aislamiento & purificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Riesgo , España/epidemiologíaRESUMEN
La trombocitopenia inmune primaria, anteriormente conocida como púrpura trombocitopénica inmune, es una enfermedad cuyo manejo diagnóstico y terapéutico ha sido siempre controvertido. La Sociedad Española de Hematología y Oncología Pediátricas, a través del grupo de trabajo de la PTI, ha actualizado el documento con las recomendaciones protocolizadas para el diagnóstico y tratamiento de esta enfermedad, basándose en las guías clínicas disponibles actualmente, revisiones bibliográficas, ensayos clínicos y el consenso de sus miembros. El objetivo principal es disminuir la variabilidad clínica en los procedimientos diagnósticos y terapéuticos con el fin de obtener los mejores resultados clínicos, con menor incidencia en la calidad de vida y los mínimos efectos adversos (AU)
Primary immune thrombocytopenia (ITP), formerly known as immune thrombocytopenic purpura, is a disease in which clinical and therapeutic management has always been controversial. The ITP working group of the Spanish Society of Paediatric Haematology and Oncology has updated its guidelines for diagnosis and treatment of ITP in children based on current guidelines, literature review, clinical trials and member consensus. The primary objective was to lessen clinical variability in diagnostic and therapeutic procedures in order to obtain best clinical results with minimal adverse events and good quality of life (AU)
Asunto(s)
Humanos , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Pautas de la Práctica en MedicinaRESUMEN
Primary immune thrombocytopenia (ITP), formerly known as immune thrombocytopenic purpura, is a disease in which clinical and therapeutic management has always been controversial. The ITP working group of the Spanish Society of Paediatric Haematology and Oncology has updated its guidelines for diagnosis and treatment of ITP in children based on current guidelines, literature review, clinical trials and member consensus. The primary objective was to lessen clinical variability in diagnostic and therapeutic procedures in order to obtain best clinical results with minimal adverse events and good quality of life.
Asunto(s)
Púrpura Trombocitopénica/diagnóstico , Protocolos Clínicos , Árboles de Decisión , Humanos , Púrpura Trombocitopénica/inmunología , Púrpura Trombocitopénica/terapiaRESUMEN
We describe a severe case of hemophagocytic lymphohistiocytosis (HLH), secondary to a candida glabrata retroperitoneal abscess in a 41-year-old simultaneous pancreas-kidney transplantation (SPKT) recipient. Despite percutaneous abscess drainage and antifungal therapy, general status deteriorated with persistent fever, severe pancytopenia and liver dysfunction. Presence of hypertriglyceridemia, very high serum levels of ferritin and hemophagocytosis in a bone-marrow aspirate gave the diagnosis of HLH. Of note, change from tacrolimus to cyclosporine together with dexamethasone produced rapid response with status improvement. We concluded that HLH, a rare but often fatal condition characterized by excessive activation of lymphocytes and macrophages, is a diagnostic and therapeutic challenge in solid-organ transplanted patients and must be suspected in the presence of fever, blood cytopenia and liver dysfunction. Specific antiinfectious therapy together with cyclosporine and dexamethasone may be a therapeutic approach.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antifúngicos/uso terapéutico , Ciclosporina/uso terapéutico , Dexametasona/uso terapéutico , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Adulto , Candida glabrata , Candidiasis/complicaciones , Candidiasis/diagnóstico , Candidiasis/tratamiento farmacológico , Humanos , Trasplante de Riñón/efectos adversos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/etiología , Masculino , Trasplante de Páncreas/efectos adversosRESUMEN
Objetivos: Describir las manifestaciones visuales en neoplasias neuropediátricas, relacionarlas con la localización tumoral y analizar su relevancia en el seguimiento de la enfermedad. Material y métodos: Estudio descriptivo retrospectivo que incluye pacientes menores de 14 años con neoplasias cerebrales de cualquier estirpe, registradas en nuestro centro desde 1996 hasta el 2005. Resultados: En un 44% de los pacientes con descenso en la agudeza visual, la ambliopía fue catalogada como orgánica. En el 28% de los casos, la ambliopía era secundaria al estrabismo/nistagmus producido por el tumor. El tratamiento corrector resultó efectivo en varios casos de ambliopía parcial y totalmente orgánica. Tres recidivas tumorales fueron detectadas gracias a la exploración de fondo de ojo y campimetría, antes de que las pruebas de imagen fueran concluyentes. Conclusión: El examen oftalmológico (agudeza visual, campimetría, funduscopia) es una pieza clave en el seguimiento de la patología tumoral cerebral. Las ambliopías orgánicas parciales/totales son susceptibles de tratamiento corrector
Purposes: To describe the visual manifestations of brain neoplasms, and to analyze the effect of tumor control on these. Methods: This is a descriptive retrospective study, which includes patients under 14 years of age, suffering from different brain neoplasms in our hospital between 1996 and 2005 inclusive. Results: In the group of patients with low visual acuity, 44% had organic amblyopias. In 28% of cases, the amblyopia was secondary to the strabismus/nystagmus produced by the developing tumor. Corrective treatment was successful in some cases of partial or total organic amblyopia. Ophthalmologic evaluation (including perimetry and fundoscopy) enabled detection of 3 tumor relapses. Conclusions: Visual analysis (visual acuity, perimetry, fundoscopy) should be an essential component of assessment during brain neoplasm treatment and follow-up. Corrective treatment is sometimes successful in organic amblyopias (Arch Soc Esp Oftalmol 2008; 83: 471-478)
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Niño , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico , Fondo de Ojo , Pruebas del Campo Visual/métodos , Pruebas del Campo Visual/tendencias , Astrocitoma/complicaciones , Astrocitoma/diagnóstico , Estudios Retrospectivos , Oftalmoscopía , Tomografía Computarizada de EmisiónRESUMEN
PURPOSES: To describe the visual manifestations of brain neoplasms, and to analyze the effect of tumor control on these. METHODS: This is a descriptive retrospective study, which includes patients under 14 years of age, suffering from different brain neoplasms in our hospital between 1996 and 2005 inclusive. RESULTS: In the group of patients with low visual acuity, 44% had organic amblyopias. In 28% of cases, the amblyopia was secondary to the strabismus/nystagmus produced by the developing tumor. Corrective treatment was successful in some cases of partial or total organic amblyopia. Ophthalmologic evaluation (including perimetry and fundoscopy) enabled detection of 3 tumor relapses. CONCLUSIONS: Visual analysis (visual acuity, perimetry, fundoscopy) should be an essential component of assessment during brain neoplasm treatment and follow-up. Corrective treatment is sometimes successful in organic amblyopias
Asunto(s)
Astrocitoma/complicaciones , Neoplasias Encefálicas/complicaciones , Oftalmopatías/etiología , Fondo de Ojo , Trastornos de la Visión/etiología , Agudeza Visual , Pruebas del Campo Visual , Adolescente , Factores de Edad , Ambliopía/etiología , Astrocitoma/diagnóstico , Astrocitoma/epidemiología , Astrocitoma/terapia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/terapia , Niño , Preescolar , Oftalmopatías/diagnóstico , Estudios de Seguimiento , Humanos , Hiperopía/diagnóstico , Hiperopía/etiología , Lactante , Recién Nacido , Nistagmo Patológico/diagnóstico , Nistagmo Patológico/etiología , Estudios Retrospectivos , Estrabismo/etiología , Trastornos de la Visión/diagnóstico , Campos VisualesRESUMEN
Kikuchi-Fujimoto disease is an uncommon form of lymphadenitis, firstly described in Japan. Etiology is unknown. It affects mainly young women. It commonly manifests as a painful cervical lymphadenitis usually associated with fever and leukopenia. Clinical course users to be benign, leading spontaneously to a complete recovery. Histological findings include necrotizing changes with cariorrhesis, partial loss of ganglionar architecture and foci of histiocytic infiltrates in the cortical and/or paracortical zones of the lymph nodes. A common finding is the absence of neutrophil granulocytes in the inflammatory infiltrates, in contrast to other necrotizing lymphadenitis. We report four cases of Kikuchi-Fujimoto disease, recently identified in our hospital.
Asunto(s)
Linfadenitis Necrotizante Histiocítica/diagnóstico , Adulto , Niño , Diagnóstico Diferencial , Femenino , Humanos , MasculinoRESUMEN
La enfermedad de Kikuchi Fujimoto es una forma inusual de linfadenitis observada inicialmente en Japón. La etiología es desconocida y afecta preferentemente a mujeres jóvenes en forma de linfadenitis cervical dolorosa asociado con frecuencia fiebre y leucopenia. Se trata de una enfermedad benigna y de resolución espontánea. La lesión histológica se caracteriza por fenómenos necróticos con cariorrexis, pérdida parcial de la estructura ganglionar y focos de histiocitos en la zona cortical y/o paracortical. Un hallazgo característico es la ausencia de granulocitos neutrófilos, lo que la diferencia de otras linfadenitis necrotizantes. Recogemos cuatro casos de enfermedad de Kikuchi-Fujimoto atendidos en nuestro centro en un año. Tres pacientes eran adultos y el otro una niña en edad pediátrica. La mitad referían fiebre y los cuatro tuvieron adenopatías. La evolución fue buena en todos. Pensamos que la enfermedad de Kikuchi-Fujimoto es probablemente más frecuente en nuestro país que lo recogido en la literatura
Kikuchi Fujimoto disease is an uncommon form of lymphadenitis, firstly described in Japan. Etiology is unknown. It affects mainly young women. It commonly manifests as a painful cervical lymphadenitis usually associated with fever and leukopenia. Clinical course users to be benign, leading spontaneously to a complet recovery. Histological findings include necrotizing changes with cariorrhesis, partial loss of ganglionar architecture and foci of histiocytic infiltrates in the cortical and/or paracortical zones of the lymph nodes. A common findings is the absence of neutrophil granulocytes in the inflammatory infiltrates, in contrast to other necrotizing lymphadenitis. We report four cases of Kikuchi Fujimoto disease, recently identified in our hospital
Asunto(s)
Masculino , Femenino , Adulto , Niño , Humanos , Estudios de Casos y Controles , Linfadenitis Necrotizante Histiocítica/complicaciones , Linfadenitis Necrotizante Histiocítica/diagnóstico , Linfadenitis Necrotizante Histiocítica/terapia , Linfadenitis/diagnóstico , Linfadenitis/terapia , Diagnóstico Diferencial , Leucopenia/complicaciones , Granulocitos/patología , Enfermedades Linfáticas/diagnóstico , Enfermedades Linfáticas/epidemiología , Enfermedades Linfáticas/terapiaRESUMEN
Varicella vaccine has shown its efficacy to prevent the disease and complications in healthy and immunodeficient children. In this article the authors evaluate the immunologic status of acute lymphoblastic leukaemia at diagnosis and at follow up and the development of chickenpox and/or herpes zoster. Children with negative serology and continuous complete remission of acute lymphoblastic leukaemia for one year were vaccinated. Of 71 children diagnosed of acute lymphoblastic leukaemia from 1983 to 1996, 25 received the vaccine and seroconversion was obtained in 76% after one dose and 92% after the second dose. Vaccine tolerance was adequate. The incidence of herpes zoster infection was decreased in vaccinated children during chemotherapy compared to the wild-virus infected ones. Nowadays that vaccine for healthy children is recommended, we consider a priority to protect from chickenpox the children affected by leukaemia that are in continuous complete remission of the disease.
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Vacuna contra la Varicela/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Varicela/prevención & control , Vacuna contra la Varicela/administración & dosificación , Niño , Preescolar , Femenino , Herpes Zóster , Humanos , Lactante , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Inducción de RemisiónRESUMEN
Interferon-alpha (IFN-alpha) is a biological response modifier with antiviral and tumoral effect that is used in the treatment of chronic myelogenous leukemias. Adverse effects are well documented and cardiovascular disturbances mostly include hypotension and tachycardia and rarely cardiomyopathy. We report on an infant with chronic myelomonocytic leukemia (CML) diagnosed at 3 months of age who was treated with increasing IFN-alpha dosage (2.5-5.5 million U/m2/day) given subcutaneously for 7.5 months. At that age, he presented anorexia, general malaise, and nocturnal sweating for about a week, followed by respiratory distress and tachycardia. Diagnosis of congestive heart failure was suspected and documented by cardiomegaly and echographic changes of left ventricular dilated cardiomyopathy, with a 40% left ventricular ejection fraction (EF) and 20% fractional shortening (FS). He was treated with digoxin, furosemide, and angiotensin converting inhibitors, and IFN-alpha was discontinued. Progressive improvement of cardiac function was observed within 7 months of the events with normalization of the echocardiographic findings (EF 60%, FS 31%). We should emphasize the possibility of severe and reversible cardiac toxicity of IFN-alpha in infancy.
Asunto(s)
Antineoplásicos/efectos adversos , Cardiomiopatía Dilatada/inducido químicamente , Interferón-alfa/efectos adversos , Antineoplásicos/uso terapéutico , Cardiomiopatía Dilatada/diagnóstico por imagen , Cardiomiopatía Dilatada/tratamiento farmacológico , Cardiotónicos/uso terapéutico , Relación Dosis-Respuesta a Droga , Ecocardiografía , Estudios de Seguimiento , Hemodinámica/efectos de los fármacos , Humanos , Lactante , Interferón-alfa/uso terapéutico , Leucemia Mielomonocítica Crónica/diagnóstico , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Masculino , Resultado del TratamientoRESUMEN
We report the case of a 2-year-old boy with hypereosinophilia who presented with fever, muscle pain and heart, CNS and skin involvement. He was treated with steroids with partial response. Six months after diagnosis of hypereosinophilia, several scalp nodules were surgically removed and Hypoderma bovis larvae were found, which led to the diagnosis of cutaneous myiasis. Following removal of the larvae, the clinical and hematological manifestations returned to normal.
Asunto(s)
Eosinofilia/etiología , Hipodermosis/complicaciones , Animales , Preescolar , Dípteros , Humanos , MasculinoRESUMEN
UNLABELLED: Fetal hydrops associated with neonatal tumours is an uncommon occurrence. The diagnosis can be established prenatally by ultrasound examination. The treatment of choice is surgery which may be curative. We report the case of a male born at 32 weeks gestation who presented with severe hydrops fetalis and a thoracic mass. The child could not be operated upon because of rapid clinical deterioration. The autopsy findings confirmed the diagnosis of congenital fibrosarcoma. This is, to our knowledge, the first case of hydrops fetalis associated with fibrosarcoma. CONCLUSION: The association of hydrops fetalis and fibrosarcoma is an exceptional observation but can be added to the long list of differential diagnoses of non-immune hydrops.