Characteristics of bleeding in children with hemophilia in a reference center in Colombia

Introducción: La hemofilia es el trastorno hemorrágico congénito más frecuente en los varones, los pacientes con enfermedad severa pueden tener sangrados espontáneos que llevan a discapacidad. Objetivo: Describir las características de los sangrados y los aspectos clínicos y demográficos de un grupo de pacientes con diagnóstico de hemofilia en un centro de referencia de la ciudad de Bogotá. Materiales y métodos: Estudio descriptivo de serie de casos, en menores de 18 años con hemofilia, entre mayo 1 a diciembre 31 de 2014. Resultados: Se incluyeron 51 pacientes, 33/51 tuvieron sangrado, 109 sangrados, el sangrado más frecuente fue hemartrosis y en niños con anticuerpos inhibidores. 22 pacientes tenían hemofilia severa, 18 moderada y 11 leve. 18/22 pacientes severos sangraron y tuvieron 87 sangrados, 14/18 (77%) pacientes con artropatía tuvieron sangrado, con 74 eventos en total, 19/33 pacientes sin artropatía tuvieron 35 eventos. El grupo con mayor frecuencia de sangrados tenía entre 5 y 9 años. De los 81 episodios traumáticos, la mayoría fueron jugando y haciendo deporte; Se presentaron 19 sangrados espontáneos y nueve relacionados con procedimientos. 84 sangrados fueron en temporada escolar y 25 en vacaciones. Al momento de los sangrados en 76 episodios estaban acompañados por padres o familiares y 69 episodios ocurrieron en el hogar (62,4%). Conclusiones: Los sangrados fueron más frecuentes en niños con anticuerpos inhibidores, enfermedad severa, con artropatía, en temporada escolar y estando acompañados. No hubo mayor frecuencia de sangrados en aquellos con disfunción familiar.Introduction: Hemophilia is the most common congenital hemorrhagic disorder in males. Patients with severe disease may have spontaneous bleeding leading to disability. Objective: To describe the bleedings and clinical features of children diagnosed with hemophilia and treated in a reference center in Bogotá. Methodology:Descriptive study of a case series of children (under 18 years) diagnosed with hemophilia, between May 1st and December 31th 2014. Results: Fifty-one patients were included, 33/51 experienced 109 bleedings. Most common type were  hemarthrosis and children with inhibitory antibodies had more bleeding episodes. Twenty-two patients had severe hemophilia, 18 moderate and 11 mild. In 18 of 22 severe patients, there were 87 bleeding episodes. 14/33 patients with arthropathy (77%) experienced 74 bleeding events while the rest referred only 35. Patients between 5 to 9 years old had the highest frequency of bleeding. Among the 81 traumatic episodes, most frequent activities were playing and sport practicing; there were 19 spontaneous bleedings and nine were related to procedures. 89 bleeds occurred during school days and 25 on vacation. At the time of bleeding, in 76 episodes, patients were accompanied by family members. Conclusions: Bleeding was more frequent in children with severe disease, with arthropathy, during school time and while being accompanied. Bleedings did not occurred with a higher frequency in children with family dysfunction

Intensive chemotherapy in children with acute lymphoblastic leukemia. Interim analysis in a referral center in Colombia.

Background: Acute lymphoblastic leukemia is the most common cancer in children. In developed countries, overall survival rates are around 80%, while in developing countries, survival rate is much lower due to high rates of relapse, and abandonment and complications arising from the disease treatment.Objectives: To assess induction mortality, relapse and treatment abandonment. To describe the most frequent side effects of chemotherapy. To evaluate survival rates of patients and compare the findings found in this study with the existing literature.Material and methods: A retrospective cohort study was conducted on patients aged 1 to 18 with acute lymphoblastic leukemia, who received treatment under the BFM ALL IC 2009 protocol at Fundación Hospital La Misericordia (HOMI), from November 2012 to December 2014.Results: 119 patients were included. Death occurred in two cases during induction (1.67%) and in nine (7.7%) due to treatment, all of them caused by infection/sepsis and in complete remission. Six patients abandoned treatment (5%), while seven relapses occurred (5.9%). All patients experienced some type of side effect related to chemotherapy, the most frequent being febrile neutropenia (41.2%) and grade 3-4 infections (15.8%). Overall survival and event-free survival rates were 79.9% and 73.3%, respectively.Conclusions: Evaluating complications of treatment and death allows adopting measures and strategies to reduce such complications.Introducción. La leucemia linfoblástica aguda es el cáncer más frecuente en los niños. La sobrevida en países desarrollados está alrededor de 80%, mientras que en países de bajos ingresos la tasa de supervivencia es menor debido a altas cifras de recaída, abandono de tratamiento y complicaciones relacionadas con el tratamiento. Objetivos. Hacer una evaluación de muerte en inducción relacionada con el tratamiento, las recaídas y los abandonos de tratamiento; describir las reacciones adversas más observadas relacionadas con medicamentos de quimioterapia; evaluar la sobrevida, y comparar los hallazgos con publicaciones previas.Materiales y métodos. Estudio de cohorte retrospectivo. Se incluyeron pacientes con edades entre 1 y 18 años, con diagnóstico de leucemia linfoblástica aguda tratada entre noviembre de 2012 y diciembre de 2014 en la Fundación Hospital La Misericordia de Bogotá (HOMI) y a quienes se les había aplicado tratamiento con el protocolo BFM ALL IC 2009.Resultados. Se incluyeron 119 pacientes. Se presentaron dos (1.67%) muertes en inducción y nueve (7.7%) relacionadas con tratamiento —todas por infección/sepsis y en remisión completa—, seis abandonos (5%) y siete recaídas (5.9%). Todos los pacientes presentaron algún tipo de reacción adversa relacionada con medicamentos de quimioterapia, las más frecuentes fueron neutropenia febril (41.2%) e infecciones grado 3-4 (15.8%). Las sobrevidas global y libre de evento fueron de 79.9% y 73.3%, respectivamente.Conclusiones. La evaluación de los efectos deletéreos del tratamiento y muerte durante tratamiento permiten tomar medidas para disminuir estas complicaciones

Costo-efectividad de 18fdg-pet/ct vs ct al final del tratamiento en pacientes pediátricos con linfoma hodgkin

Objetivo Estimar la costo-efectividad de 18FDG-PET/CT comparado con CT seguido de 18FDG-PET/CT como prueba confirmatoria de un caso positivo en la evaluación al final del tratamiento en pacientes menores de 18 años con Linfoma Hodgkin (LH).Métodos Se construyó un árbol de decisión donde se comparó el uso de 18FDGPET/CT con CT seguido de 18FDG-PET/CT como prueba confirmatoria de un caso positivo en la detección de lesión residual. El resultado se midió en Años de Vida Ganados (AVG). Se calculó la razón de costo-efectividad incremental. Se utilizó como umbral 3 veces el PIB per cápita por año AVG. Valores expresados en pesos colombianos de 2010 (1 US dólar = $1 897,89) Se realizaron análisis de sensibilidad univariados, bivariados y probabilísticos.Resultados Suponiendo un diferencial en AVG entre verdaderos positivos y falsos negativos de 13 meses, el costo de un AVG adicional con 18FDG-ET/CTcomparado con CT seguido de 18FDG-PET/CT como prueba confirmatoria de un caso positivo en la evaluación al final del tratamiento en pacientes pediátricos con LH fue$ 34 508 590.Conclusión Si el diferencial de esperanza de vida entre verdaderos positivos y falsos negativos es de al menos un 1,03 años, el uso de 18FDG-PET/CT en la evaluación al final del tratamiento de pacientes pediátricos con LH, es una estrategia costo-efectiva para Colombia

Results of the 2006 ACHOP protocol on children with acute lymphoblastic leukemia at the HOMI Hospital of Misericordia Foundation in Bogotá in the period 2007 to 2012

Introduction: Acute leukemia is the most common neoplasm in children, accounting for approximately 25% of all tumors in childhood. In Colombia the cure proportion, around 50%, are lower than reported in developed countries. Objective: The main bjective is to determine the global and event-free survival of children with diagnosis of lymphoblastic leukemia, all treated with the ACHOP Protocol 2006, from 2007 to 2012. The secondary objectives are to describe mortality, abandonment, relapse and major complications related to treatment. Material and methods: A descriptive cohort study of 183 patients under 18 years of age, with a confirmed diagnosis of acute lymphoblastic leukemia, who were treated at the Foundation of the Misericordia (HOMI) from 2007 to 2012, was performed. The survival dates were obtained by analysis with Kaplan-Meier curves. Results: We analyzed overall survival at 2, 3 and 5 years with results of 89%, 87.3% and 74.7 % (95% CI 67 - 80.9) respectively. At 5 years survival for the standard risk group was 78.6 % (95 % CI 68.3-85.1) and 61.9 % (95 % CI 50.7-73) for the high risk group. The event-free survival, considering the abandonment and transfer to another institution as an event, was 56.3 % (95% CI 45.5 - 65.8) at 5 years. Mortality in induction was 3.8 %, mortality related to treatment was 3.4 %, 32 patients (17 %) relapsed, bandonment was 16.4 % and transfers 10.4 %. The main complication of the treatment was infections. Conclusions: Overall survival is acceptable for a country with limited resources, the events of abandonment and transfers are very high. Efforts should be made to reduce these situations that worsen the prognosis of the disease

Tumores germinales gonadales en niños: experiencia de 20 años en un centro de referencia pediátrico.

Antecedentes. Los tumores de células germinales son un grupo heterogéneo de neoplasias que corresponden al 1-3% de los tumores en pediatría. Por lo general, se manifiestan clínicamente con masa testicular o dolor abdominal.Objetivo. Describir las características de los pacientes con tumores germinales gonadales en un centro de referencia de cáncer pediátrico en Colombia.Materiales y métodos. Este artículo hace una revisión retrospectiva recopilando 20 años de experiencia en el diagnóstico y manejo de estos tumores en la Fundación Hospital de la Misericordia.Resultados. Se encontraron 79 pacientes, 35 hombres y 44 mujeres, con un promedio de edad, al diagnóstico, de 6 años. El teratoma fue la neoplasia más frecuente en el sexo femenino y el tumor del seno endodérmico en el masculino. El 70,9% de los pacientes se diagnosticaron en estadio I; se tienen datos de marcadores tumorales en 84,8%. El 98,7% se manejaron con cirugía y 58,2% recibieron además quimioterapia, especialmente protocolo BEP. 96% alcanzaron remisión de la enfermedad, 3 pacientes fallecieron.Conclusiones. El estudio demuestra buenos resultados en el manejo de los tumores germinales gonadales con el protocolo establecido de manejo quirúrgico y quimioterapia, se encontró una baja tasa de recurrencia en el periodo evaluado y alto porcentaje de niños libres de enfermedad.Background. Germ cell tumors are a heterogeneous group of neoplasms corresponding to 1-3% of pediatric tumors. They usually manifest clinically as testicular mass or abdominal pain.Objective. To make a description of gonadal germ cell tumor types in pediatric referral center in Colombia.Materials and methods. This article takes a retrospective review compiling 20 years of experience in diagnosis and management of these tumors in the Fundación Hospital de La Misericordia.Results. We found 79 patients, 35 men and 44 women, with an average age at diagnosis of 6 years. The teratoma was the most common neoplasia in females and endodermal sinus tumor in men. 70.9% of patients were diagnosed with stage I. In 84,8% measuring tumor markers were obtained. 98.7% were managed with surgery and 58.2% also received chemotherapy, especially BEP protocol. 96% achieved disease remission, 3 patients died.Conclusions. The study shows good results in the management of gonadal germ cell tumors with the established protocol and low recurrence rate in the evaluated period and high rates of children free of disease, were found a low rate of recurrence in the assessment period and high percentage of free of disease

Tumores germinales gonadales en niños: experiencia de 20 años en un centro de referencia pediátrico.

Antecedentes. Los tumores de células germinales son un grupo heterogéneo de neoplasias que corresponden al 1-3% de los tumores en pediatría. Por lo general, se manifiestan clínicamente con masa testicular o dolor abdominal.Objetivo. Describir las características de los pacientes con tumores germinales gonadales en un centro de referencia de cáncer pediátrico en Colombia.Materiales y métodos. Este artículo hace una revisión retrospectiva recopilando 20 años de experiencia en el diagnóstico y manejo de estos tumores en la Fundación Hospital de la Misericordia.Resultados. Se encontraron 79 pacientes, 35 hombres y 44 mujeres, con un promedio de edad, al diagnóstico, de 6 años. El teratoma fue la neoplasia más frecuente en el sexo femenino y el tumor del seno endodérmico en el masculino. El 70,9% de los pacientes se diagnosticaron en estadio I; se tienen datos de marcadores tumorales en 84,8%. El 98,7% se manejaron con cirugía y 58,2% recibieron además quimioterapia, especialmente protocolo BEP. 96% alcanzaron remisión de la enfermedad, 3 pacientes fallecieron.Conclusiones. El estudio demuestra buenos resultados en el manejo de los tumores germinales gonadales con el protocolo establecido de manejo quirúrgico y quimioterapia, se encontró una baja tasa de recurrencia en el periodo evaluado y alto porcentaje de niños libres de enfermedad.Background. Germ cell tumors are a heterogeneous group of neoplasms corresponding to 1-3% of pediatric tumors. They usually manifest clinically as testicular mass or abdominal pain.Objective. To make a description of gonadal germ cell tumor types in pediatric referral center in Colombia.Materials and methods. This article takes a retrospective review compiling 20 years of experience in diagnosis and management of these tumors in the Fundación Hospital de La Misericordia.Results. We found 79 patients, 35 men and 44 women, with an average age at diagnosis of 6 years. The teratoma was the most common neoplasia in females and endodermal sinus tumor in men. 70.9% of patients were diagnosed with stage I. In 84,8% measuring tumor markers were obtained. 98.7% were managed with surgery and 58.2% also received chemotherapy, especially BEP protocol. 96% achieved disease remission, 3 patients died.Conclusions. The study shows good results in the management of gonadal germ cell tumors with the established protocol and low recurrence rate in the evaluated period and high rates of children free of disease, were found a low rate of recurrence in the assessment period and high percentage of free of disease

Intensive chemotherapy in children with acute lymphoblastic leukemia. Interim analysis in a referral center in Colombia.

Background: Acute lymphoblastic leukemia is the most common cancer in children. In developed countries, overall survival rates are around 80%, while in developing countries, survival rate is much lower due to high rates of relapse, and abandonment and complications arising from the disease treatment. Objectives: To assess induction mortality, relapse and treatment abandonment. To describe the most frequent side effects of chemotherapy. To evaluate survival rates of patients and compare the findings found in this study with the existing literature. Material and methods: A retrospective cohort study was conducted on patients aged 1 to 18 with acute lymphoblastic leukemia, who received treatment under the BFM ALL IC 2009 protocol at Fundación Hospital La Misericordia (HOMI), from November 2012 to December 2014. Results: 119 patients were included. Death occurred in two cases during induction (1.67%) and in nine (7.7%) due to treatment, all of them caused by infection/sepsis and in complete remission. Six patients abandoned treatment (5%), while seven relapses occurred (5.9%). All patients experienced some type of side effect related to chemotherapy, the most frequent being febrile neutropenia (41.2%) and grade 3-4 infections (15.8%). Overall survival and event-free survival rates were 79.9% and 73.3%, respectively. Conclusions: Evaluating complications of treatment and death allows adopting measures and strategies to reduce such complications

Hypothalamus-pituitary-adrenal axis suppression following induction chemotherapy in children with acute lymphoblastic leukemia

Background: Adrenal insufficiency has been reported in 46 % to 81.5 % of children receiving corticosteroids for acute lymphoblastic leukemia (ALL). Methodology: To assess the frequency of such insufficiency, 40 patients under 18 years (mean: 8.5 years) with new diagnosis of ALL were studied. Base-line cortisol and adrenocorticotropin (ACTH) levels were measured, and they received 5-week therapy with prednisolone. After 3 days off-steroid therapy, a stimulation test with ACTH 1 μg was done. In patients with abnormal cortisol (<18 μg/dL) new ACTH tests were done and cortisol levels were determined at days 7, 14 and 30 until cortisol post-stimulation levels were normal. Results: Three days after the last steroid dose 29/40 (72.5 %) had adrenal insufficiency after ACTH stimulus. At day 30 no one had abnormal cortisol levels after ACTH stimulus. All patients with adrenal suppression were over 5 years (HR 4.69; CI95 %: 1.44-15.32; p = 0.011). Conclusion: Steroids used during ALL treatment may cause adrenal insufficiency. Patients over 5 years are at high risk of developing adrenal suppression. We suggest to follow-up those patients with stress episodes after induction chemotherapy as steroid supplementation may be indicated

Sensitization to Drug Treatment in Precursor B-Cell Acute Lymphoblastic Leukemia Is Not Achieved by Stromal NF-κB Inhibition of Cell Adhesion but by Stromal PKC-Dependent Inhibition of ABC Transporters Activity

Cell adhesion to stromal support and the associated intracellular signaling are central to drug resistance, therefore blocking both has been effective in increasing drug sensitization in leukemia. The stromal Ser/Thr protein kinase C (PKC) has been found to be important for conferring protection to leukemic cells. We aimed at elucidating the intracellular signals connected to cell adhesion and to stromal PKC. We found that NF-κB and Akt were up-regulated in mesenchymal stem cells (MSC) after binding of B-cell acute lymphoblastic leukemia (B-ALL) cells. Nevertheless, Akt inhibition did not induce B-ALL cell detachment. In spite of a clear activation of the NF-κB signaling pathway after B-ALL cell binding (up-regulation NF-κB1/2, and down-regulation of the IKBε and IKBα inhibitors) and an important reduction in cell adhesion after NF-κB inhibition, sensitization to the drug treatment was not observed. This was opposite to the PKC inhibitors Enzastaurin and HKPS, a novel chimeric peptide inhibitor, that were able to increase sensitization to dexamethasone, methotrexate, and vincristine. PLCγ1, Erk1/2, and CREB appear to be related to PKC signaling and PKC effect on drug sensitization since they were contra-regulated by HKPS when compared to dexamethasone-treated cells. Additionally, PKC inhibition by HKPS, but not by Enzastaurin, in MSC reduced the activity of three ABC transporters in leukemic cells treated with dexamethasone, a new indirect mechanism to increase sensitization to drug treatment in B-ALL cells. Our results show the validity of targeting the functional characteristic acquired and modulated during cell-to-cell interactions occurring in the leukemic niche

Evaluation of the diagnostic performance of platelet-derived indices for the differential diagnosis of thrombocytopenia in pediatrics

Background. Platelet-derived indices have a well-established correlation with the differential diagnosis of thrombocytopenia in adult-based research. These indices include mean platelet volume, platelet distribution width, and platelet-large cell ratio. Objective. To determine the values of platelet-derived indices in a pediatric population with diagnoses of thrombocytopenia and their etiologic correlation. Materials and methods. Analytic observational diagnostictest study. The population for this analytical study was pediatric patients between 6 months and 18 years of age who had thrombocytopenia (<100x109/L). The study period was 18 months long. Results. Of 54 subjects, 18 (33.3%) were diagnosed with idiopathic thrombocytopenic purpura, and 36 (66.7%) were diagnosed with acute leukemia. Mean age was 7.4 years and 6.8 years for immune thrombocytopenic purpura and acute leukemia, respectively. Mean platelet distribution width values for immune thrombocytopenic purpura and acute leukemia were 15.08 fL and 10.73, respectively. Mean MPV for immune thrombocytopenic purpura and acute leukemia was 11.7 fL and 9.8 fL, respectively. Mean platelet-large cell ratio was 38.26% and 24.97% for idiopathic thrombocytopenic purpura and acute leukemia, respectively. Differences in these three distinct platelet indices between idiopathic thrombocytopenic purpura and acute leukemia were statistically significant (p=0.00). The area under the ROC curve for platelet-derived indices showed that they were adequate for defining the causes of thrombocytopenia. MPV and platelet-large cell ratio had an area under the curve of 0.89 and 0.88, respectively, while platelet size deviation width had an area under the curve of 0.903. Conclusions. Platelet-derived indices could be useful in the initial approach for the differential diagnosis of pediatric patients with thrombocytopenia