Younger age and induction failure predict outcomes in infant leukemia: 30 years of experience in a tertiary center.

Objectives: This study aimed to evaluate the characteristics and outcomes of infant patients with leukemia. Methods: A retrospective analysis was conducted in a cohort of 39 patients diagnosed with infant leukemia from 1990 to 2020 who underwent treatment at the pediatric hemato-oncology department of a tertiary hospital in Madrid, Spain. Results: Of the 588 diagnosed cases of childhood leukemia, 39 (6.6%) cases were infant leukemia. The 5-year event-free survival and the 5-year overall survival were 43.6% (SE 4.1) and 46.5% (SD 24.08), respectively. In a univariate analysis, a younger age at diagnosis was associated with poorer outcomes (p = 0.027), as was induction failure (p = 0.0024). Patients treated with hematopoietic stem cell transplantation had better outcomes than non-transplanted patients (p = 0.001); however, the group comparisons that exclude patients who were unable to undergo transplantation due to refractoriness/relapse or death during treatment showed no significant differences. Conclusions: The main risk factors that affected survival in our study were an age younger than 6 months and a poor response to induction therapy. It is important to identify poor prognostic factors in this population in order to seek different approaches that could improve outcomes.

Advanced Molecular Characterisation in Relapsed and Refractory Paediatric Acute Leukaemia, the Key for Personalised Medicine.

Relapsed and refractory (R/r) disease in paediatric acute leukaemia remains the first reason for treatment failure. Advances in molecular characterisation can ameliorate the identification of genetic biomarkers treatment strategies for this disease, especially in high-risk patients. The purpose of this study was to analyse a cohort of R/r children diagnosed with acute lymphoblastic (ALL) or myeloid (AML) leukaemia in order to offer them a targeted treatment if available. Advanced molecular characterisation of 26 patients diagnosed with R/r disease was performed using NGS, MLPA, and RT-qPCR. The clinical relevance of the identified alterations was discussed in a multidisciplinary molecular tumour board (MTB). A total of 18 (69.2%) patients were diagnosed with B-ALL, 4 (15.4%) with T-ALL, 3 (11.5%) with AML and 1 patient (3.8%) with a mixed-phenotype acute leukaemia (MPL). Most of the patients had relapsed disease (88%) at the time of sample collection. A total of 17 patients (65.4%) were found to be carriers of a druggable molecular alteration, 8 of whom (47%) received targeted therapy, 7 (87.5%) of them in addition to hematopoietic stem cell transplantation (HSCT). Treatment response and disease control were achieved in 4 patients (50%). In conclusion, advanced molecular characterisation and MTB can improve treatment and outcome in paediatric R/r acute leukaemias.

Haploidentical hematopoietic stem cell transplantation in pediatric and adolescent patients: A study of the Spanish hematopoietic stem cell transplantation group (GETH).

INTRODUCTION: The main advantages of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) are the immediate availability of donors, the possibility of developing cell therapy approaches with different novel transplant platforms, and the procedure's cost savings. METHODOLOGY: We retrospectively analyzed the pediatric haplo-HSCT activity of the Spanish hematopoietic stem-cell transplantation group (GETH) between 1999 and 2016, aiming to study clinical characteristics and outcomes by describing patient groups with non-malignant disease (NMD) or malignant disease (MD) and the impact of 2 different periods (1999-2009 and 2010-2016) on long-term outcomes. RESULTS: Twelve centers performed 232 haplo-HSCTs in 227 children, representing 10% of all pediatric allogeneic HSCT activity in Spain from 1999 to 2016, with a notable increase since 2013. Most haplo-HSCTs (86.7%) were performed in patients with MD; 95% received peripheral blood stem cells from donors, and 78.9% received ex vivo T-cell depleted grafts. Non-manipulated grafts using post-transplantation cyclophosphamide have been incorporated since 2012. We observed a higher percentage of graft failure in NMD versus MD (32% vs. 15.6%; p=0.029). Relapse and transplant-related mortality were the procedure's main limitations in MD and NMD, respectively. Five-year overall survival was 48.5% (SE 3.9), with no statistically significant difference when comparing the MD and NMD cohorts. Patients who received previously a HSCT the overall survival was significantly decreased. We observed no survival improvement over time. CONCLUSIONS: Although haplo-HSCT is an increasingly employed treatment option, our patients' results need improvement. We need to develop reference centers, especially for NMD whose rarity makes it difficult to gain experience.

Urgent Bordetella PCR in infants under 3 months, a useful tool in the Pediatric Emergency Department. / PCR urgente de Bordetella en lactantes menores de 3 meses, una herramienta útil en el Servicio de Urgencias Pediátricas.

INTRODUCTION: Whooping cough in patients aged under 3 months has higher rates of morbimortality. Hospitalization and treatment with azithromycin is generally recommended. Many patients with cough without other signs of alarm, are admitted and started antibiotic therapy until a result of Bordetella-PCR is available. This technique, when performed urgently, can provide the diagnosis in a few hours. The objective of this study is to determine if its generalisation in the Emergency Department allows to improve patient management. METHODS: Retrospective cohort study of patients aged under 3 months who underwent Bordetella-PCR testing from upper respiratory tract secretions since March 2011 to December 2017. From December 2015 the test was performed urgently. RESULTS: One hundred and fifty-eight PCR were performed, 16 (10%) were positive for B. pertussis. Negative results (142; 90%) were divided in 2 cohorts: conventional-PCR, with 74 cases, and urgent-PCR, with 68 cases. The 2 groups were homogeneous in terms of clinical and analytical characteristics. In the urgent-PCR group there was 18% reduction in chest X-rays performed (P=.008). There were 33 (48.5%) patients admitted in the urgent-PCR group, compared to 49 (66.2%) in the conventional-PCR (P=.042). Antibiotic treatment was initiated in 32% of the patients in the urgent-PCR group compared to 67% in the conventional-PCR group (P=.000047), without observing any significant increase in the number of visits to the Emergency Department or worse clinical performance. CONCLUSIONS: The introduction of urgent PCR in the Emergency Department is a useful tool in the management of infants under 3 months of age with suspected pertussis, since it can avoid unnecessary admissions, diagnostic tests and antibiotic treatments.

Vólvulo intestinal en niños de edad escolar: reto diagnóstico en urgencias / Intestinal volvulus in school-age children: an emergency care challenge

El dolor abdominal supone uno de los motivos de consulta más frecuentes en los Servicios de Urgencias Pediátricas. El vólvulo intestinal es una entidad infrecuente pero que sin un diagnóstico y tratamiento quirúrgico precoces tiene consecuencias devastadoras, siendo una de las urgencias que todos los pediatras deben conocer. Los vólvulos suponen hasta el 14% de las causas de síndrome de intestino corto que pueden llegar a precisar trasplante intestinal. Requiere un alto índice de sospecha, ya que las pruebas complementarias pueden ser inespecíficas y su normalidad no descarta esta patología. Únicamente la intervención quirúrgica confirma el diagnóstico de vólvulo intestinal. Presentamos los casos de cuatro pacientes que acudieron al Servicio de Urgencias y fueron diagnosticados de vólvulo intestinal. (AU)

Abdominal pain is one of the most frequent reasons for visiting paediatric emergency departments. Intestinal volvulus is an infrequent condition, but without early diagnosis and surgical treatment it has devastating consequences, and it is one of the emergencies that paediatricians must be aware of. Intestinal volvulus accounts for up to 14% short bowel syndrome cases that may require bowel transplantation. A high level of suspicion must be maintained, as the results of diagnostic tests may be nonspecific and normal results do not rule it out. Surgical intervention is the only way to confirm the diagnosis of intestinal volvulus. We present the cases of 4 patients who attended the emergency department and received a diagnosis of volvulus. (AU)

PCR urgente de Bordetella en lactantes menores de 3 meses, una herramienta útil en el Servicio de Urgencias Pediátricas / Urgent Bordetella PCR in infants under 3 months, a useful tool in the Pediatric Emergency Department

Introducción: En pacientes menores de 3 meses con sospecha de tosferina se recomienda ingreso y tratamiento con azitromicina debido a su mayor morbimortalidad, por lo que muchos pacientes con tos sin otros signos de alarma ingresan con antibioterapia hasta obtener el resultado de la PCR de Bordetella. La realización de esta técnica de forma urgente proporciona el diagnóstico en pocas horas. Nuestro objetivo fue determinar si su introducción en los servicios de Urgencias mejoraba el manejo de estos pacientes. Métodos: Estudio de cohortes histórico de pacientes menores de 3 meses a los que se realizó en Urgencias la PCR de Bordetella de secreciones respiratorias desde marzo de 2011 hasta diciembre de 2017. A partir de diciembre de 2015 era procesada de forma urgente. Resultados: Se realizaron 158 PCR, 16 (10%) de las cuales resultaron positivas para B. pertussis. Los resultados negativos (142; 90%) se dividen en 2 grupos de estudio: PCR-convencional, con 74 casos, y PCR-urgente, con 68 casos. Los 2 grupos son homogéneos en cuanto a características clínicas y analíticas. En el grupo PCR-urgente se realizaron un 18% menos de radiografías de tórax (p=0,008) e ingresaron 33 pacientes (48,5%), frente a 49 (66,2%) en el grupo PCR-convencional (p=0,042). Recibió tratamiento antibiótico el 32% en el grupo PCR-urgente frente al 67% en el PCR-convencional (p=0,000047), sin aumento significativo de las reconsultas en Urgencias ni peor evolución. Conclusiones: La PCR urgente de Bordetella es una herramienta útil en los servicios de Urgencias para el manejo de los lactantes menores de 3 meses con sospecha de tosferina, ya que puede evitar ingresos, pruebas y tratamientos antibióticos innecesarios.(AU)

Introduction: Whooping cough in patients aged under 3 months has higher rates of morbimortality. Hospitalization and treatment with azithromycin is generally recommended. Many patients with cough without other signs of alarm, are admitted and started antibiotic therapy until a result of Bordetella-PCR is available. This technique, when performed urgently, can provide the diagnosis in a few hours. The objective of this study is to determine if its generalisation in the Emergency Department allows to improve patient management. Methods: Retrospective cohort study of patients aged under 3 months who underwent Bordetella-PCR testing from upper respiratory tract secretions since March 2011 to December 2017. From December 2015 the test was performed urgently. Results: One hundred and fifty-eight PCR were performed, 16 (10%) were positive for B. pertussis. Negative results (142; 90%) were divided in 2 cohorts: conventional-PCR, with 74 cases, and urgent-PCR, with 68 cases. The 2 groups were homogeneous in terms of clinical and analytical characteristics. In the urgent-PCR group there was 18% reduction in chest X-rays performed (P=.008). There were 33 (48.5%) patients admitted in the urgent-PCR group, compared to 49 (66.2%) in the conventional-PCR (P=.042). Antibiotic treatment was initiated in 32% of the patients in the urgent-PCR group compared to 67% in the conventional-PCR group (P=.000047), without observing any significant increase in the number of visits to the Emergency Department or worse clinical performance. Conclusions: The introduction of urgent PCR in the Emergency Department is a useful tool in the management of infants under 3 months of age with suspected pertussis, since it can avoid unnecessary admissions, diagnostic tests and antibiotic treatments.(AU)

Haploidentical hematopoietic stem cell transplantation in pediatric and adolescent patients: A study of the Spanish hematopoietic stem cell transplantation group (GETH)

Introduction: The main advantages of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) are the immediate availability of donors, the possibility of developing cell therapy approaches with different novel transplant platforms, and the procedure's cost savings.MethodologyWe retrospectively analyzed the pediatric haplo-HSCT activity of the Spanish hematopoietic stem-cell transplantation group (GETH) between 1999 and 2016, aiming to study clinical characteristics and outcomes by describing patient groups with non-malignant disease (NMD) or malignant disease (MD) and the impact of 2 different periods (1999–2009 and 2010–2016) on long-term outcomes.ResultsTwelve centers performed 232 haplo-HSCTs in 227 children, representing 10% of all pediatric allogeneic HSCT activity in Spain from 1999 to 2016, with a notable increase since 2013. Most haplo-HSCTs (86.7%) were performed in patients with MD; 95% received peripheral blood stem cells from donors, and 78.9% received ex vivo T-cell depleted grafts. Non-manipulated grafts using post-transplantation cyclophosphamide have been incorporated since 2012. We observed a higher percentage of graft failure in NMD versus MD (32% vs. 15.6%; p=0.029). Relapse and transplant-related mortality were the procedure's main limitations in MD and NMD, respectively. Five-year overall survival was 48.5% (SE 3.9), with no statistically significant difference when comparing the MD and NMD cohorts. Patients who received previously a HSCT the overall survival was significantly decreased. We observed no survival improvement over time.ConclusionsAlthough haplo-HSCT is an increasingly employed treatment option, our patients’ results need improvement. We need to develop reference centers, especially for NMD whose rarity makes it difficult to gain experience. (AU)

Introducción: Las principales ventajas del trasplante de progenitores hematopoyéticos de donante haploidéntico (haplo-TPH) son la disponibilidad inmediata de donantes, la posibilidad de desarrollar terapia celular postrasplante y el ahorro de costes al obviar el proceso de búsqueda de donante.MetodologíaAnalizamos retrospectivamente la actividad haplo-TPH en población pediátrica del grupo español de trasplante hematopoyético (GETH) entre 1999 y 2016, con el objetivo de estudiar las características clínicas y los resultados mediante la descripción de grupos de pacientes con enfermedad no malignas (ENM) o enfermedad maligna (EM) y el impacto de dos períodos diferentes (1999-2009 y 2010-2016) en los resultados a largo plazo.ResultadosDoce centros realizaron 232 haplo-TPH en 227 niños, lo que representa el 10% de toda la actividad de TPH alogénicos pediátricos en España entre 1999-2016, con un aumento notable desde 2013. La mayoría de los haplo-TPH (86,7%) se realizaron en pacientes con EM; el 95% recibió progenitores hematopoyéticos de sangre periférica y el 78,9% recibió injertos con purgado de células T ex vivo. Los injertos no manipulados con ciclofosfamida postrasplante se realizaron a partir de 2012. Observamos un mayor porcentaje de fallos del injerto en la ENM que en la EM (32% frente a 15,6%; p=0,029). La recaída y la mortalidad relacionada con el trasplante fueron las principales limitaciones del procedimiento en la EM y la ENM, respectivamente. La supervivencia global a cinco años fue del 48,5% (EE 3,9), sin diferencias estadísticamente significativas al comparar las cohortes con EM y ENM. En los pacientes que recibieron previamente un TPH, la supervivencia global se redujo significativamente. No observamos mejoría en la supervivencia a lo largo del tiempo. (AU)