The paediatric cancer clinical research landscape in Spain: a 13-year multicentre experience of the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP)

Purpose Early phase trials are crucial in developing innovative effective agents for childhood malignancies. We report the activity in early phase paediatric oncology trials in Spain from its beginning to the present time and incorporate longitudinal data to evaluate the trends in trial characteristics and recruitment rates. Methods Members of SEHOP were contacted to obtain information about the open trials at their institutions. The study period was split into two equal periods for analysis: 2007–2013 and 2014–2020. Results Eighty-one trials and two molecular platforms have been initiated. The number of trials has increased over the time of the study for all tumour types, with a predominance of trials available for solid tumours (66%). The number of trials addressed to tumours harbouring specific molecular alterations has doubled during the second period. The proportion of industry-sponsored compared to academic trials has increased over the same years. A total of 565 children and adolescents were included, with an increasing trend over the study period. For international trials, the median time between the first country study approval and the Spanish competent authority approval was 2 months (IQR 0–6.5). Fourteen out of 81 trials were sponsored by Spanish academic institutions. Conclusions The number of available trials, and the number of participating patients, has increased in Spain from 2007. Studies focused on molecular-specific targets are now being implemented. Barriers to accessing new drugs for all ranges of age and cancer diseases remain. Additionally, opportunities to improve academic research are still required in Spain (AU)

The paediatric cancer clinical research landscape in Spain: a 13-year multicentre experience of the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP).

PURPOSE: Early phase trials are crucial in developing innovative effective agents for childhood malignancies. We report the activity in early phase paediatric oncology trials in Spain from its beginning to the present time and incorporate longitudinal data to evaluate the trends in trial characteristics and recruitment rates. METHODS: Members of SEHOP were contacted to obtain information about the open trials at their institutions. The study period was split into two equal periods for analysis: 2007-2013 and 2014-2020. RESULTS: Eighty-one trials and two molecular platforms have been initiated. The number of trials has increased over the time of the study for all tumour types, with a predominance of trials available for solid tumours (66%). The number of trials addressed to tumours harbouring specific molecular alterations has doubled during the second period. The proportion of industry-sponsored compared to academic trials has increased over the same years. A total of 565 children and adolescents were included, with an increasing trend over the study period. For international trials, the median time between the first country study approval and the Spanish competent authority approval was 2 months (IQR 0-6.5). Fourteen out of 81 trials were sponsored by Spanish academic institutions. CONCLUSIONS: The number of available trials, and the number of participating patients, has increased in Spain from 2007. Studies focused on molecular-specific targets are now being implemented. Barriers to accessing new drugs for all ranges of age and cancer diseases remain. Additionally, opportunities to improve academic research are still required in Spain.

Resultados del trasplante de progenitores hematopoyéticos en hemoglobinopatías: talasemia maior y enfermedad drepanocítica / Results of hematopoietic stem cell transplantation in hemoglobinopathies: Thalassemia major and sickle cell disease

Introducción: La prevalencia de las hemoglobinopatías en nuestro medio ha aumentado como consecuencia de los flujos migratorios. La talasemia mayor cursa con anemia hemolítica crónica y necesidad de transfusiones regulares desde el año de vida. La enfermedad drepanocítica cursa con anemia, vasculopatía y daño orgánico progresivo. En ambas, la esperanza de vida está disminuida. El trasplante alogénico de progenitores hematopoyéticos es una opción de curación para estos pacientes. Pacientes: Diecisiete pacientes recibieron un trasplante alogénico de progenitores hematopoyéticos: 14 afectados de talasemia maior y 3 de enfermedad drepanocítica. Resultados: Los donantes fueron en los pacientes con talasemia mayor 9 hermanos HLA-idénticos, 2 progenitores con una diferencia antigénica HLA y 3 donantes no emparentados, y en aquellos con enfermedad drepanocítica, 3 hermanos HLA-idénticos. La fuente fue la médula ósea en todos, excepto uno. La media de edad al trasplante de progenitores hematopoyéticos fue de 6 años (intervalo: 1-16) en los niños con talasemia mayor y doce años (intervalo: 8-15) en los niños con enfermedad drepanocítica. Se confirmó injerto medular en todos los pacientes. Dos con talasemia mayor presentaron fallo de injerto secundario, precisando nuevamente soporte transfusional. Trece pacientes presentaron quimerismo completo y 2 quimerismo mixto, todos con normalización de la cifra de hemoglobina y sin requerimiento de transfusiones. Los pacientes con enfermedad drepanocítica no presentaron más episodios vasooclusivos y la funciones pulmonar y cerebral en aquellos pacientes que presentaban afectación en el momento del trasplante se estabilizaron. Tres pacientes con talasemia mayor desarrollaron enfermedad injerto contra huésped crónica y 5, hipogonadismo hipogonadotropo. Conclusiones: Nuestra experiencia confirma que el trasplante alogénico de progenitores hematopoyéticos de hermano HLA idéntico es una buena opción en el tratamiento de la talasemia mayor y la enfermedad drepanocítica. En el caso de la talasemia mayor, el trasplante de donante no emparentado es una opción terapéutica en centros especializados, ya que, a pesar de los buenos resultados presentados, la morbimortalidad de este procedimiento puede ser elevada, frente a la alternativa de un tratamiento médico no curativo pero con expectativas de supervivencia prolongada. En el caso de la enfermedad drepanocítica, el trasplante de donante no emparentado todavía está en fases preliminares de investigación (AU)

Background: The prevalence of hemoglobinopathies in Spain is increasing as a result of immigration. Thalassemia major presents with chronic hemolytic anemia that requires regular red blood cell transfusions within the first year of life. Patients with sickle cell disease suffer from chronic anemia, vasculopathy and progressive damage in almost any organ. There is decreased life expectancy in both conditions. Allogeneic hematopoietic stem cell transplantation represents the only potentially curative option. Patients: Seventeen patients (fourteen thalassemia major, and three sickle cell disease) underwent allogeneic hematopoietic stem cell transplantations. Results: In the thalassemia group, nine donors were HLA-geno-identical siblings, two were partially matched related donors (one HLA allele mismatch), and three unrelated donors. All three patients with sickle cell disease were transplanted from HLA-geno-identical siblings. The source of stem cells was bone marrow in sixteen cases. Median patient age at transplant was six years (range: 1–16) in the thalassemia group, and twelve years (range: 8–15) in the sickle cell disease group. The graft was successful in all patients. Secondary graft rejection was observed in two thalassemia patients rendering them dependent on blood transfusions. Complete chimerism was observed in thirteen patients and, although mixed chimerism occurred in two, with all of them showing normal hemoglobin levels after transplantation and not requiring further transfusion support. Patients affected by sickle cell disease did not present with new vaso-occlusive crises, and stabilization of pulmonary and neurological function was observed. Chronic graft-versus-host disease was detected in three patients affected by thalassemia, and hypogonadotrophic hypogonadism in five patients. Conclusions: We conclude that for thalassemia major and sickle cell disease, allogenic hematopoietic stem cell transplantation from HLA-geno-identical siblings offers a high probability of complication-free survival. Despite good results, morbidity and mortality associated with transplantation from unrelated donors is a risk that might be considered, in contrast to a non-curative medical treatment that offers a long term survival. For thalassemia major groups it could be an option, but not for sickle cell disease, which is still in the investigational phase (AU)

Randomized clinical trial comparing endoscopic treatment with dextranomer hyaluronic acid copolymer and Cohen's ureteral reimplantation for vesicoureteral reflux: long-term results.

PURPOSE: To compare efficacy of Cohen's ureteral reimplantation and endoscopic treatment with Dx/HA in patients with primary VUR grades II, III and IV. METHODS: From April 2002 to June 2004, patients over 1 year old with VUR grade I, II, III or IV were included. Patients were randomized into two groups: endoscopic treatment (ET) or ureteral reimplantation (UR). In the ET group, an ultrasonography study was performed 24 h and 1 month after surgery, and two voiding cystourethrographies at 3 and 6 months post treatment. In the UR group, an ultrasonography study was done 7 days and 1 month after surgery and a micturial cystography 6 months post surgery. A postoperative nuclear direct cystogram was performed 5 years later in both groups. RESULTS: A total of 41 patients were included in this study: in ET 22 patients with 35 refluxing ureters and in UR 19 patients with 32 refluxing ureters. The VUR grades in ET were: 16 grade II, 16 grade III and 3 grade IV; and in UR: 15 grade II, 12 grade III and 5 grade IV. VUR was resolved in 91% (32/35) of ET (28% of ureters needed a second injection), and in 100% of UR group. Five years after the procedure, VUR was still resolved in 30/32 of ET and 32/32 of UR. CONCLUSION: Short- and long-term follow up shows that multiple endoscopic treatment of VUR grades II, III and IV with Dx/HA is as effective as ureteral reimplantation.

[Results of hematopoietic stem cell transplantation in hemoglobinopathies: thalassemia major and sickle cell disease]. / Resultados del trasplante de progenitores hematopoyéticos en hemoglobinopatías: talasemia maior y enfermedad drepanocítica.

BACKGROUND: The prevalence of hemoglobinopathies in Spain is increasing as a result of immigration. Thalassemia major presents with chronic hemolytic anemia that requires regular red blood cell transfusions within the first year of life. Patients with sickle cell disease suffer from chronic anemia, vasculopathy and progressive damage in almost any organ. There is decreased life expectancy in both conditions. Allogeneic hematopoietic stem cell transplantation represents the only potentially curative option. PATIENTS: Seventeen patients (fourteen thalassemia major, and three sickle cell disease) underwent allogeneic hematopoietic stem cell transplantations. RESULTS: In the thalassemia group, nine donors were HLA-geno-identical siblings, two were partially matched related donors (one HLA allele mismatch), and three unrelated donors. All three patients with sickle cell disease were transplanted from HLA-geno-identical siblings. The source of stem cells was bone marrow in sixteen cases. Median patient age at transplant was six years (range: 1-16) in the thalassemia group, and twelve years (range: 8-15) in the sickle cell disease group. The graft was successful in all patients. Secondary graft rejection was observed in two thalassemia patients rendering them dependent on blood transfusions. Complete chimerism was observed in thirteen patients and, although mixed chimerism occurred in two, with all of them showing normal hemoglobin levels after transplantation and not requiring further transfusion support. Patients affected by sickle cell disease did not present with new vaso-occlusive crises, and stabilization of pulmonary and neurological function was observed. Chronic graft-versus-host disease was detected in three patients affected by thalassemia, and hypogonadotrophic hypogonadism in five patients. CONCLUSIONS: We conclude that for thalassemia major and sickle cell disease, allogenic hematopoietic stem cell transplantation from HLA-geno-identical siblings offers a high probability of complication-free survival. Despite good results, morbidity and mortality associated with transplantation from unrelated donors is a risk that might be considered, in contrast to a non-curative medical treatment that offers a long term survival. For thalassemia major groups it could be an option, but not for sickle cell disease, which is still in the investigational phase.

Neutropenia congénita grave: análisis de las características clínicas, estudios diagnósticos, tratamiento y seguimiento a largo plazo / Severe congenital neutropenia: analysis of clinical features, diagnostic methods, treatment and long-term outcome

Introducción: La NCG es una entidad heterogénea que se manifiesta en edades precoces de la vida y se caracteriza por un fallo primario en la mielopoyesis con un RAN < 0,5 x 109/l, infecciones graves y riesgo de transformación leucémica. Objetivo: Conocer el curso evolutivo a largo plazo de los pacientes diagnosticados de NCG. Material y métodos: Se analizaron las características clínicas, los métodos diagnósticos, el tratamiento y la evolución de 11 pacientes afectados de NCG. Resultados: La mediana de edad al diagnóstico fue de 4 meses (rango: 3 días-12 años). Clínica inicial en todos los casos: infección grave. Mediana de RAN al diagnóstico: 0,2 x 109/l (rango: 0-0,37). El aspirado de médula ósea mostró en todos los casos stop madurativo a nivel de promielocito. El estudio genético mostró en 3 mutaciones, 2 que afectaban al gen ELA2 y una en el gen G6PC3. El G-CSF fue el tratamiento de elección en 9 pacientes. Seis presentaron una buena respuesta a las dosis de entre 5-15 μg/kg/día administrado de 3 a 7días por semana. Tres no respondieron a G-CSF, indicándose un TPH alogénico. En 2 pacientes el TPH fue el tratamiento de primera elección. Mediana de seguimiento de 5 años (rango: 1-10), con una supervivencia del 100% sin ningún caso de transformación leucémica. Conclusiones: A la vista de los datos podemos concluir que el estudio genético de la NCG es útil para establecer una correlación entre genotipo y fenotipo. El tratamiento de elección es la administración G-CSF por vía subcutánea, al que responden las dos terceras partes de los pacientes, indicándose el TPH para los casos de mala respuesta o en aquellos que evolucionan a SMD o leucemia, por lo que el seguimiento de esta entidad es fundamental (AU)

Introduction: Severe congenital neutropenia (SCN), a heterogeneous condition with onset at early ages, is characterised by primary myelopoiesis failure with an absolute neutrophil count (ANC) < 0.5 x109/L, severe infections and risk of leukaemic transformation. Objective: The aim of the study was to ascertain the long term outcome of patients with SCN. Material and methods: The clinical features, diagnostic methods, treatment and outcome of 11 patients with SCN were analysed. Results: The median age at diagnosis was 4 months (range: 3 days-12 years). The primary clinical manifestation was severe infection. Median ANC at diagnosis: 0.2 x 109/L (range: 0-0.37). Bone marrow aspirate showed maturation arrest at promyelocyte stage in all cases. Genetic studies revealed 3 mutations, two in ELA-2 gene and 1 in G6PC3 gene, showing a correlation between genotype and phenotype. Granulocyte Colony Stimulating Factor (G-CSF) was the first-line treatment in 9 patients; six of whom showed a good response at doses between 5 and 15 μg/kg/day for 3-7 days/week. The remaining 3 patients failed to respond to G-CSF and allogeneic stem cell transplantation (SCT) was indicated. Furthermore, SCT was the treatment of choice in two cases. Median follow-up of the cohort was 5 years (range: 1-10 years) with 100% survival and no cases of leukaemic transformation. Conclusions: We conclude that genetic study is useful for establishing a correlation between genotype and phenotype. The treatment of choice for SCN is G-CSF to which 2/3 of patients should respond; while SCT is reserved for cases of poor response or those evolving to myelodysplastic syndrome (MDS) or leukaemia; thus close follow-up of this condition is essential (AU)

[Severe congenital neutropenia: analysis of clinical features, diagnostic methods, treatment and long-term outcome]. / Neutropenia congénita grave: análisis de las características clínicas, estudios diagnósticos, tratamiento y seguimiento a largo plazo.

INTRODUCTION: Severe congenital neutropenia (SCN), a heterogeneous condition with onset at early ages, is characterised by primary myelopoiesis failure with an absolute neutrophil count (ANC) < 0.5 x10(9)/L, severe infections and risk of leukaemic transformation. OBJECTIVE: The aim of the study was to ascertain the long term outcome of patients with SCN. MATERIAL AND METHODS: The clinical features, diagnostic methods, treatment and outcome of 11 patients with SCN were analysed. RESULTS: The median age at diagnosis was 4 months (range: 3 days-12 years). The primary clinical manifestation was severe infection. Median ANC at diagnosis: 0.2 x 10(9)/L (range: 0-0.37). Bone marrow aspirate showed maturation arrest at promyelocyte stage in all cases. Genetic studies revealed 3 mutations, two in ELA-2 gene and 1 in G6PC3 gene, showing a correlation between genotype and phenotype. Granulocyte Colony Stimulating Factor (G-CSF) was the first-line treatment in 9 patients; six of whom showed a good response at doses between 5 and 15 µg/kg/day for 3-7 days/week. The remaining 3 patients failed to respond to G-CSF and allogeneic stem cell transplantation (SCT) was indicated. Furthermore, SCT was the treatment of choice in two cases. Median follow-up of the cohort was 5 years (range: 1-10 years) with 100% survival and no cases of leukaemic transformation. CONCLUSIONS: We conclude that genetic study is useful for establishing a correlation between genotype and phenotype. The treatment of choice for SCN is G-CSF to which 2/3 of patients should respond; while SCT is reserved for cases of poor response or those evolving to myelodysplastic syndrome (MDS) or leukaemia; thus close follow-up of this condition is essential.

Protocolo de estudio y tratamiento de la trombocitopenia inmune primaria (PTI-2010) / Protocol for the study and treatment of Immune Thrombocytopenic Purpura (ITP). ITP-2010

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)

Glomerulonefritis aguda asociada a neumonía: revisión de 6 casos / Pneumonia associated acute glomerulonephritis: a review of 6 cases

Introducción: Se ha descrito una asociación entre neumonía y glomerulonefritis aguda iniciándose ambos procesos de forma simultánea. Pacientes y métodos: Estudio retrospectivo de 6 pacientes ingresados en nuestro centro entre los años 2001 y 2010 con glomerulonefritis aguda asociada a neumonía concomitante, con frotis y cultivo amigdalar negativos y en ausencia de infección cutánea o episodio de neumonía anterior. Resultados: La media de edad de los pacientes al ingreso fue de 5,9 años sin diferencia de sexos. El diagnóstico de neumonía se realizó en el momento del ingreso, coincidiendo con la sintomatología nefrológica. Los síntomas más frecuentes fueron fiebre y hematuria macroscópica. Todos tuvieron un C3 (fracción C3 del complemento) bajo. En 5 de ellos se encontró una elevación significativa en la cifra de antiestreptolisinas (ASLO). En la mayoría de los casos la afectación renal fue leve a excepción de un caso de insuficiencia renal aguda con creatinina inicial de 2,77 mg/dl y filtrado glomerular de 27 ml/min/1,73m2 y 2 casos con proteinuria en rango nefrótico. Todos evolucionaron hacia la curación sin tratamiento o con mínimo tratamiento diurético o hipotensor, además de tratamiento antibiótico adecuado para su proceso neumónico, con resolución de la clínica entre 7—10 días y normalización del C3 en un período inferior a los 4 meses. Conclusiones: Aunque descrita con mucho menos frecuencia, existe asociación entre glomerulonefritis aguda y presencia concomitante de neumonía. Las ASLO, en nuestra serie, no son específicas de infección por Streptococcus pyogenes. El pronóstico respiratorio y renal fue favorable en todos los casos (AU)

Introduction: There is an association between pneumonia and acute glomerulonephritis. Both processes start simultaneously. Patients and methods: A retrospective study of 6 patients admitted to our centre between 2001 and 2010 with acute glomeruolonephritis associated with pneumonia. The result of the smear and tonsil culture was negative and there was an absence of cutaneous infection. Results: The average age of the patients on admission was 5.9 years with no differences in sex. The diagnosis for pneumonia was made at the time of admission, coinciding with the glomerular symptoms. The most frequent symptoms were fever and macrohaematuria. All had low levels of C3. A significant increase in ASLO was found in 5 cases. The majority of the cases had mild symptoms with the exception of one case of acute renal failure with an initial creatinine of 2.77 mg/dL and glomerular filtration rate of 27 ml/min/1.73m2, and two cases with proteinuria in the nephrotic range. All of them progressed satisfactorily without treatment or with minimum diuretic or hypotensive treatment in addition to the appropriate antibiotic treatment with clinical resolution in 7 to 10 days, and C3 returning to normal within a period of less than 4months. Conclusions: There is an association between acute glomerulonephritis and pneumonia, although it is very uncommon. The ASLOs in our series are not specific for Streptoccocus. Pyogenes infection. The respiratory and renal prognosis was favourable in all cases (AU)

[Protocol for the study and treatment of immune thrombocytopenic purpura (ITP). ITP-2010]. / Protocolo de estudio y tratamiento de la trombocitopenia inmune primaria (PTI-2010).

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.

[Pneumonia associated acute glomerulonephritis: a review of 6 cases]. / Glomerulonefritis aguda asociada a neumonía: revisión de 6 casos.

INTRODUCTION: There is an association between pneumonia and acute glomerulonephritis. Both processes start simultaneously. PATIENTS AND METHODS: A retrospective study of 6 patients admitted to our centre between 2001 and 2010 with acute glomeruolonephritis associated with pneumonia. The result of the smear and tonsil culture was negative and there was an absence of cutaneous infection. RESULTS: The average age of the patients on admission was 5.9 years with no differences in sex. The diagnosis for pneumonia was made at the time of admission, coinciding with the glomerular symptoms. The most frequent symptoms were fever and macrohaematuria. All had low levels of C3. A significant increase in ASLO was found in 5 cases. The majority of the cases had mild symptoms with the exception of one case of acute renal failure with an initial creatinine of 2.77mg/dL and glomerular filtration rate of 27ml/min/1.73m(2), and two cases with proteinuria in the nephrotic range. All of them progressed satisfactorily without treatment or with minimum diuretic or hypotensive treatment in addition to the appropriate antibiotic treatment with clinical resolution in 7 to 10 days, and C3 returning to normal within a period of less than 4 months. CONCLUSIONS: There is an association between acute glomerulonephritis and pneumonia, although it is very uncommon. The ASLOs in our series are not specific for Streptoccocus. pyogenes infection. The respiratory and renal prognosis was favourable in all cases.

Resultados de una serie de biopsias renales percutáneas guiadas ecográficamente en una población pediátrica: nuestra experiencia en 15 años / Results obtained from a series of ultrasound guided percutaneous renal biopsies in a pediatric population: our experience in 15 years

Objetivos: Presentar nuestra experiencia sobre biopsias renales percutáneas guiadas ecográficamente en pacientes en edad pediátrica desde que se instauró dicha técnica en nuestro hospital, y valorar la correlación clínica/anatomopatológica y las complicaciones de la misma. Pacientes y métodos: Estudio retrospectivo de 180 biopsias renales percutáneas guiadas ecográficamente realizadas a un total de 164 pacientes (de 6 meses-18 años de edad) durante un periodo de 15 años. El protocolo de la biopsia incluye su realización en el quirófano mediante sedación y una ecografía a las 24 horas. Resultados: El motivo más frecuente de su realización fue la presencia de un síndrome nefrótico cortico dependiente/resistente (29,4%), seguido de la proteinuria de diverso rango con presencia de hematuria. El diagnóstico anatomopatológico más habitual fue la glomérulo nefritis mesangial por IgA (26,1%), seguido de cambios glomerulares mínimos, confirmándose en la mayoría de los casos la sospecha clínica. Únicamente se detectó una complicación grave (hematoma renal/hipotensión arterial)en un paciente de riesgo. Conclusiones: En nuestra experiencia, la biopsia renal percutánea es un método diagnóstico fiable y seguro, independientemente de la edad (AU)

Objectives: We present our experience on ultrasound guided percutaneous renal biopsies in pediatric patients from the beginning that this technique was established in our hospital, to value the clinical/anatomo pathologic correlation as well as the complications of the technique. Patients and methods: Retrospective study of 180 ultrasound guided percutaneous renal biopsies over a total of 164 patients (aged from 6 months to 18 years) in a period of 15 years. The protocol biopsy includes its carrying out in the operating room by means of sedation and also the realization of an ultrasound after 24 hours. Results: The most frequent reason for doing the biopsy was the presence of a corticoid dependent/resistant nephrotic syndrome (29.4%) followed by different levels of. The most frequent anatomopathological diagnostic was glomerulonephritis with Ig A mesangial deposits (26.1%) followed by minimal glomerular changes, confirming in the majority of the cases the initial clinical suspicion. Only in one case a severe complication was detected (renal hematoma/arterial hypotension) in a high-risk patient. Conclusions: In our experience, the percutaneous renal biopsies are a reliable and a safe diagnostic method regardless of age (AU)

Post-transplant lymphoproliferative disorders in children: the role of chemotherapy in the era of rituximab.

PTLD are the most frequent neoplasms in children postorgan transplantation. We describe our experience in the treatment of 14 children (three with early and 11 with late-onset disease) treated with a step-wise protocol developed at our institution. Treatment consisted of reducing immunosuppressants, followed by rituximab and chemotherapy if required. Rituximab, incorporated into the protocol in 2001, has been determinant for the total chemotherapy burden patients need to achieve remission. In seven patients who did not receive rituximab, anthracycline total dose ranged from 160 to 240 mg/m(2), while only one of the patients receiving rituximab required DOXO (range: 0-120 mg/m(2)) (p = 0.003). The use of alkylating agents was also notably lower in patients receiving rituximab (median dose = 1200 mg/m(2)) compared with those who did not receive rituximab (median dose = 5800 mg/m(2)) (p = 0.006). Twelve patients are in remission and two died, one from refractory disease and the other from septic shock. Two-year OS and EFS were 85.7% and 57%, respectively. In conclusion, our experience with the use of rituximab in children with PTLD after solid organ transplantation appeared to be associated with a lesser requirement for alkylating agents and anthracyclines compared with historical subjects, suggesting a reduction in the side effects of these agents.

Hipertensión arterial por esfuerzo: posible predictor de riesgo cardiovascular / Exercise-induced arterial hypertension: possible predictor of cardiovascular risk

Introducción: Durante el ejercicio se produce una elevación fisiológica de la presión arterial. Algunos sujetos previamente normotensos presentan grandes incrementos con el ejercicio, lo que podría ser un factor pronóstico adverso.Casos clínicos: Dos varones de 15 y 16 años, sin antecedentes personales de interés, remitidos por pérdida de conciencia de minutos de duración, en el primer caso, con recuperación espontánea mientras entrenaba al baloncesto y, en el segundo, con cefalea importante desencadenada durante un partido de fútbol. Se constataron cifras de presión > P99 en ambos. La exploración física era normal. Se realizaron determinaciones en condiciones de reposo, que mostraron intervalos de normalidad. Los hallazgos analíticos, función renal, metabólica y hormonal fueron normales. No se encontraron anomalías en la eco-Doppler. Se descartó afección de órganos diana. La monitorización ambulatoria de la presión arterial mostró máximos de presión > P99 coincidiendo con la realización de ejercicio; las demás lecturas estaban dentro de la normalidad. Se suprimió el ejercicio físico intenso sin requerir otro tipo de medidas.Conclusiones: Valorar la aparición de hipertensión arterial en adolescentes que practican deporte, introducir la monitorización ambulatoria de la presión arterial como cribado en revisiones médico-deportivas y suprimir el esfuerzo como única medida terapéutica(AU)

Introduction: Exercise produces a physiological increase of the blood pressure. Some previously normotensive subjects have significant increases with exercise, which could be an adverse prognostic factor.Clinical cases: Two male subjects, 15 and 16 years old, with no personal background of interest, were referred. The first one was due to loss of consciousness for several minutes with spontaneous recovery while practicing basketball. The second case was for a strong headache that occurred while playing soccer. Blood pressure values for both were > P99 and their physical examinations were normal. Tests performed at rest showed normal ranges. The laboratory findings, renal and metabolic function and hormones were normal. There were no abnormalities on the echo-Doppler. Involvement of target organs was ruled out. Ambulatory blood pressure monitoring showed tension peaks > P99, coinciding with exercise, the remaining readings being within normality. Intense physical exercise was discontinued, without requiring any other type of actions.Conclusions: Introducing ambulatory blood pressure monitoring as screening in medicalsports check-ups and suppression of exercise as the only therapeutic measures should be evaluated when faced with arterial hypertension in adolescents who practice sports(AU)

[Hemolytic-uraemic syndrome. A review of 58 cases]. / Síndrome hemolítico-urémico. Revisión de 58 casos.

OBJECTIVES: Our objectives were to determine epidemiology, clinical and laboratory characteristics of patients with haemolytic-uraemic syndrome (HUS) treated in our centre, to describe renal and extra-renal complications and the treatment required and to relate our findings with the existing bibliography. METHODS: We performed a 33-year retrospective review. We included all patients diagnosed with HUS and monitored in our hospital from January 1974 to August 2007. Clinical histories and imaging studies were reviewed. RESULTS: A total of 58 patients were included in our study, with a mean age of 2 years 11 months and most of them were admitted to hospital in summer. Familial hypocomplementaemia was present in one case. A total of 48 patients presented with typical HUS (with diarrhoea D+ HUS). Salmonella enteritidis and Escherichia coli O157:H7 were isolated from those patients. While 7 cases presented with atypical HUS (without diarrhoea, D- HUS), most of them associated with a respiratory tract infection due to Streptococcus. In one case platelet count was normal. Kidney biopsy was performed in 18 patients and 25 cases underwent peritoneal dialysis. As regards complications, one child with D+ HUS experienced renal cortical necrosis and required kidney transplant, while in the D-HUS group, the patient with familial hypocomplementaemia had severe hypertension. CONCLUSIONS: a) Incidence of HUS in our environment is low. b) HUS can be present even with a normal platelet count. c) We had one case of HUS in a patient with familial hypocomplementaemia who experienced severe hypertension. d) In our group of patients, the course of the disease was not influenced by the white blood cell counts, decreased diuresis or hypocomplementaemia.

Síndrome hemolítico-urémico. Revisión de 58 casos / Hemolytic-uraemic syndrome. A review of 58 cases

Objetivos: Nuestros objetivos han sido determinar aspectos epidemiológicos, formas clínicas y analíticas de los pacientes con síndrome hemolítico-urémico (SHU) tratados en nuestros centros, así como describir las complicaciones renales y extrarrenales, el tipo de tratamiento requerido y relacionar nuestros casos con la bibliografía actual. Métodos: Efectuamos una revisión retrospectiva de la historia clínica, analítica y estudios de diagnóstico por imagen de los pacientes con diagnóstico de SHU, atendidos desde enero de 1974 hasta agosto de 2007, es decir, durante los últimos 33 años. Resultados: Un total de 58 pacientes fueron incluidos en nuestro estudio, con una edad media de 2 años y 11 meses; de ellos, estaban ingresados en verano 34 niños. Destaca la presencia de hipocomplementemia familiar en un caso. Con SHU típico (diarrea positivo [D+]) aparecieron 48 casos en los que se aislaron Salmonella enteritidis y Escherichia coli 0157:H7. Con SHU atípico (diarrea negativo [D-]) se contabilizaron 7 casos, y entre las causas destacaban procesos respiratorios de etiología estreptocócica. El recuento plaquetario fue normal en un caso. De los procedimientos empleados cabe destacar que se realizó biopsia renal en 18 pacientes y diálisis peritoneal en 25 casos. Entre las complicaciones se encontraron: en el grupo D+, un caso de necrosis cortical que requirió trasplante renal y en el grupo D-, un paciente con SHU familiar, hipocomplementemia e hipertensión arterial maligna. Conclusiones: Hemos llegado a las siguientes conclusiones: a) la enfermedad presenta una baja incidencia en nuestro medio; b) se ha detectado un caso con plaquetas normales; c) un paciente presentó SHU familiar recurrente con hipocomplementemia e hipertensión arterial grave, y d) indicadores como la leucocitosis, la oligoanuria o la hipocomplementemia no influyeron en el curso de la enfermedad (AU)

Objectives: Our objectives were to determine epidemiology, clinical and laboratory characteristics of patients with haemolytic-uraemic syndrome (HUS) treated in our centre, to describe renal and extra-renal complications and the treatment required and to relate our findings with the existing bibliography. Methods: We performed a 33-year retrospective review. We included all patients diagnosed with HUS and monitored in our hospital from January 1974 to August 2007. Clinical histories and imaging studies were reviewed. Results: A total of 58 patients were included in our study, with a mean age of 2 years 11 months and most of them were admitted to hospital in summer. Familial hypocomplementaemia was present in one case. A total of 48 patients presented with typical HUS (with diarrhoea D+ HUS). Salmonella enteritidis and Escherichia coli O157:H7 were isolated from those patients. While 7 cases presented with atypical HUS (without diarrhoea, D- HUS), most of them associated with a respiratory tract infection due to Streptococcus. In one case platelet count was normal. Kidney biopsy was performed in 18 patients and 25 cases underwent peritoneal dialysis. As regards complications, one child with D+ HUS experienced renal cortical necrosis and required kidney transplant, while in the D-HUS group, the patient with familial hypocomplementaemia had severe hypertension. Conclusions: a) Incidence of HUS in our environment is low. b) HUS can be present even with a normal platelet count. c) We had one case of HUS in a patient with familial hypocomplementaemia who experienced severe hypertension. d) In our group of patients, the course of the disease was not influenced by the white blood cell counts, decreased diuresis or hypocomplementaemia (AU)

[Neurologic presentation in haemolytic-uraemic syndrome]. / Manifestaciones neurológicas en el síndrome hemolítico urémico.

INTRODUCTION: Haemolytic-uraemic syndrome (HUS) is characterized by microangiopathic hemolytic anaemia, thrombopenia and multiorganic aggression, specially renal, gastrointestinal and central nervous system disturbances. Sporadic in Spain (2/1,500,000 inhabitants), its clinical onset includes acute renal failure, hypertension and central nervous system symptoms (irritability, drowsiness, convulsions, cortical blindness, hemiparesia or coma), due to metabolic distress, hypertension or central nervous system microangiopathy. Few long-term outcome studies have been published. PATIENTS AND METHODS: A retrospective analysis of a series of 58 patients with HUS between 1981 and 2006, is reported. Clinical onset, laboratory, electrophysiology, neuroimaging tests, and prognosis factors are reviewed, together with long-term clinical outcome. RESULTS: 22 children presented neurologic symptoms, seven had some neurological test; one patient died; in five some neurological sequelae persisted (hemiparesia, cognitive deficit, visual-perception deficit), the other 16 remaining asymptomatic. CONCLUSIONS: Neurological morbility is high in HUS (27% of the children with neurological symptoms), with a 1.7% mortality. Seizure at onset was not a poor prognosis factor in our group. No positive correlation can be established between neuroimaging and long-term outcome.

Manifestaciones neurológicas en el síndrome hemolítico urémico / Neurologic presentation in haemolytic uraemic syndrome

Introducción. El síndrome hemolítico urémico (SHU) se define como anemia hemolítica microangiopática, trombopenia y daño multiparenquimatoso fundamentalmente renal, con frecuente afectación digestiva y del sistema nervioso central. En España es esporádico (incidencia 2/1.500.000 habitantes). Las manifestaciones iniciales incluyen insuficiencia renal aguda, hipertensión arterial y sintomatología neurológica (irritabilidad, somnolencia, convulsiones, ceguera cortical, hemiparesiao coma), que puede deberse a una alteración metabólica, hipertensión arterial o microangiopatía del sistema nervioso central. Además del tratamiento específico del SHU, es fundamental la valoración y seguimiento del estado neurológico para prevenir secuelas. Existen pocas referencias bibliográficas acerca de la evolución neurológica a largo plazo. Pacientes y métodos. Estudio retrospectivo de algunos factores relacionados con el pronóstico y análisis de la evolución neurológica a largo plazo de pacientes con SHU mediante una revisión de los pacientes con SHU con manifestaciones neurológicas en fase aguda tratados en nuestro centro entre 1981 y 2006. Se analizan la clínica, analítica, estudios electrofi-siológicos y neuroimagen, y su correlación con la evolución a medio y largo plazo. Resultados. De los 58 niños con SHU, 22 presentaron síntomas neurológicos en fase aguda: en siete se realizó alguna exploración complementaria neurológica; un paciente falleció, en cinco persistió algún déficit neurológico (hemiparesia, déficit cognitivo o déficit visuoperceptivo) y 16 permanecieron asintomáticos.Conclusiones. El SHU con clínica neurológica inicial asocia una alta morbilidad (un 27% de los niños con clínica neurológica), con mortalidad del 1,7%. Las convulsiones en la fase aguda no supusieron un factor de mal pronóstico en nuestro grupo. No se puede establecer una correlación entre los hallazgos de neuroimagen y la evolución a largo plazo

Introduction. Haemolytic-uraemic syndrome (HUS) is characterized by microangiopathic hemolytic anaemia,thrombopenia and multiorganic aggression, specially renal, gastrointestinal and central nervous system disturbances. Sporadic in Spain (2/1,500,000 inhabitants), its clinical onset includes acute renal failure, hypertension and central nervous systemsymptoms (irritability, drowsiness, convulsions, cortical blindness, hemiparesia or coma), due to metabolic distress, hypertension or central nervous system microangiopathy. Few long-term outcome studies have been published. Patients and methods. A retrospective analysis of a series of 58 patients with HUS between 1981 and 2006, is reported. Clinical onset, laboratory, electrophysiology, neuroimaging tests, and prognosis factors are reviewed, together with long-term clinical outcome. Results. 22 children presented neurologic symptoms, seven had some neurological test; one patient died; in five some neurological sequelae persisted (hemiparesia, cognitive deficit, visual-perception deficit), the other 16 remaining asymptomatic.Conclusions. Neurological morbility is high in HUS (27% of the children with neurological symptoms), with a 1.7% mortality. Seizure at onset was not a poor prognosis factor in our group. No positive correlation can be established between neuroimaging and long-term outcome

Ureterohidronefrosis bilateral secundaria a hidromucocolpos de diagnóstico prenatal / Bilateral ureteral hydronephrosis secondary to prenatally diagnosed hydromucocolpos

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