Background: L-asparaginase (L-ASNase) is an essential component of chemotherapy strategies due to its differential action between normal and leukemic cells. Recently, concerns about the efficiency of commercial formulations administered in developing countries have been reported, and available methods have limitations for directly determining the quality of the formulation of the medications. Procedure:We developed a cell-based protocol to analyze the activity of different L-ASNase formulations used in Colombia to induce apoptosis of the NALM-6 cell line after 24, 48, and 72 hours, using flow cytometry. Then we compared results and determined the statistically significant differences.Results: Three statistically different groups, ranging from full to no activity against leukemic cells, using 0.05, 0.5, and 5.0 IU/ml concentrations, were identified. Group 1 (asparaginase codified [ASA]2-4) exhibited very low to no activity against B-cell acute lymphoblastic leukemia (B-ALL) cells. Group 2 (ASA6) exhibited intermediate-level activity, and group 3 (ASA1 and ASA5) exhibited high activity.Conclusions: Differences found between the therapeutic formulations of L-ASNase distributed in Colombia raise concerns about the quality of the treatment administered to patients in low-and middle-income countries. Therefore, we recommend a preclinical evaluation of formulations of L-ASNase in order to prevent therapeutical impacts on the outcome of ALL patients.
Introduction: Primary immune thrombocytopenia (ITP) is the most frequent cause of thrombocytopenia in pediatric population, with a reported incidence of 1.1-12.5 cases per 100 000 children. However, currently there are different definitions of ITP, as well as diagnostic and therapeutic approaches. Objective: To develop an evidence-based clinical practice guideline (CPG) to unify ITP definitions, and this way, reduce the variability of its diagnosis, and to provide indications for the treatment of acute, persistent, and chronic ITP in patients under 18 years of age Materials and methods: The CPG was developed by a multidisciplinary group that followed the standard methods of the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines for the development of CPGs, formulated PICO clinical questions, and conducted systematic reviews. GRADE evidence profiles were created and recommendations, with their respective level of evidence and strength, were made after a panel of experts assessed the benefit-risk balance, the quality of evidence, the patients’ values and preferences and the context in which they should be implemented. Results: A total of 23 recommendations for the treatment of acute, persistent and chronic ITP by pediatricians, hematologist and health professionals working in emergency services were made. Overall, the evidence of the GPC is of low quality and the recommendations were formulated in order to improve the treatment success rate of ITP and the prognosis of children with this condition. Conclusions: Despite ITP is the main cause of thrombocytopenia in pediatric population, so far there is not enough high quality evidence supporting the recommendations presented here for its proper classification and treatment in children. Thus, further studies providing high quality evidence on this issue are required.
Introducción. En Estados Unidos de América, entre 4 y 8% de niños con leucemias mieloides agudas tienen leucemia promielocítica aguda (LPA), mientras que en Latinoamérica se ha descrito una mayor incidencia de esta neoplasia (20%-28%). El protocolo PETHEMA LPA 99, diseñado para el tratamiento de LPA en adultos, ha mostrado una supervivencia global (SG) mayor a 80%.Objetivo. Describir los resultados de la aplicación del protocolo PETHEMA LPA 99 en el tratamiento de niños con LPA en la Fundación Hospital Pediátrico la Misericordia, en Bogotá, D.C., Colombia.Materiales y métodos. Estudio de cohorte descriptivo y retrospectivo. Se revisaron las historias clínicas de 30 pacientes pediátricos (<18 años) con LPA que recibieron tratamiento mediante el protocolo PETHEMA LPA 99 entre enero de 2005 y diciembre de 2012. Se obtuvieron datos sobre las siguientes variables: muerte temprana, muerte en terapia de inducción, SG, supervivencia libre de evento (SLE) y recaída.Resultados. De los 30 pacientes, la mayoría eran de sexo masculino (60%). Respecto a la clasificación de riesgo, 13 (43%) fueron clasificados como pacientes de riesgo alto, 12 (40%), de riesgo intermedio, y 5 (17%), de riesgo bajo. 7 individuos murieron: 2 antes del tratamiento oncológico, 2 durante la terapia de inducción, y 3 luego de presentar recaída. Se reportó recaída en 5 pacientes. No hubo muertes durante las fases de consolidación o de mantenimiento. La SG fue de 75.4% (IC95% 55.1-87.5) y la SLE fue de 64,3% (IC95% 40-80.5). La SG a 11 años fue de 80%, 91.7% y 59.2% para los pacientes de riesgo bajo, riesgo intermedio y riesgo alto, respectivamente. La mediana de seguimiento fue 6.35 años (0-11.43 años).Conclusiones. En general, la implementación del protocolo PETHEMA LPA 99 en el tratamiento de la LPA en la población de estudio mostró resultados muy satisfactorios, por lo que se recomienda su uso en población pediátrica, teniendo en cuenta los ajustes recomendados por el protocolo en relación con las características de este grupo etario.
L-asparaginase (L-ASNase) is an essential component of chemotherapy schemes due to its differential action over normal and leukemic cells. Recently, concerns on the performance of commercial formulations administered in developing countries have been reported. To address this problem, we developed a cell-based protocol to compare the activity of different L-ASNase formulations used in Colombia. We found three statistically different groups, ranging from full to no activity on leukemic cells using 0.05, 0.5 and 5.0 IU/mL concentrations. According to our results, we advise a preclinical evaluation for formulations of L-ASNase distributed in developing countries which could impact the outcome of patients.
This paper presents the case of an 11 year-old male who attended the Internal Medicine Service at a high complexity pediatric hospital.Initially, the patient attended due to a clinical profile consisting of autoimmune hemolytic anemia that was partially responsive to steroid treatment and, after exhaustive complimentary analysis, was associated to a Hodgkin lymphoma. Similar cases found in the scientific literature were reviewed in order to analyze this case.Through this paper, the authors intend to remind the medical community about the importance of a prompt and deep study of all autoimmune hemolytic anemia cases found in pediatric patients, without overlooking possible malignant causes related to this condition such as a lymphoproliferative disorder. Thus, before diagnosing a hemolytic anemia as idiopathic, the practitioner must be certain that the condition is not a clinical manifestation of an underlying disease.
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