Hiperglicemia en niños con leucemia linfoblástica aguda en tratamiento con L-asparaginasa / Evaluation and characterization of hyperglycemia in children with acute lymphoblastic leukemia treated with L-asparaginase

Introducción: L-asparaginasa (L-asp), es un agente antineoplásico, entre cuyos efectos adversos se describe hiperglicemia dado que cada molécula de insulina tiene tres residuos de asparragina que son hidrolizados por L-asp, produciendo disminución de la síntesis de insulina con la consecuente hiperglicemia. Nuestro objetivo fue describir las características de la hiperglicemia asociada al uso de L-asp en niños en tratamiento por LLA. Pacientes y Método: Estudio retrospectivo que incluyó la revisión de historias clínicas de todos los niños, ingresados al Centro Valdivia, del Programa Infantil Nacional de Drogas Antineoplásicas, entre los años 2002 y 2009. Se evaluaron los antecedentes de los pacientes y aquellos que resultaron sospechosos de reacción adversa a medicamentos, se evaluaron según el algoritmo de causalidad de Karch y Lasagna. Resultados: Ingresaron al estudio 85 de 102 pacientes que reunieron los criterios de inclusión. La incidencia de hiperglicemia fue 6,74 por ciento. Los pacientes que presentaron hiperglicemia fueron aquellos con edad mayor a 9,5 años, riesgo de obesidad, antecedentes familiares de diabetes Diabetes Mellitus y tratamiento concomitante con corticoides. Conclusión: Las características de los pacientes con hiperglicemia en tratamiento con L-asp coinciden con los de la literatura. La administración simultánea de corticoides y L-asp dificulta la determinación de causalidad de L-asp, por lo que es importante que se continúe en el futuro con esta línea de investigación.

Introduction: L-asparaginase (L-asp) is an antineoplastic agent that has among its adverse reactions, hyper-glycemia. Each insulin molecule has three asparagine residues which are hydrolyzed by L-asp, decreasing insulin synthesis and resulting in hyperglycemia. The objective of this study is to describe the characteristics of hyperglycemia associated with the use of L-asp in children with Acute Lymphoblastic Leukemia (ALL). Patients and Method: A retrospective study that included review of medical records of all children admitted to Valdivia Center of the National Children's Antineoplastic Drug Program, between 2002 and 2009 was performed. Patient backgrounds were evaluated and those who were suspected to present adverse drug reactions were evaluated according to the causality classification of Karch and Lasagna. Results: 85 of 102 patients who met the inclusion criteria entered the study. The incidence of hyperglycemia was 6.74 percent. The patients with hyperglycemia were those older than 9.5 years of age, with risk of obesity, diabetes, family history of diabetes mellitus and concomitant corticosteroid treatment. Conclusion: The characteristics of hyperglycemia in patients treated with L-asp coincide with those of the literature. Simultaneous administration of corticosteroids and L-asp make difficult to determine causality of L-asp, so further research is needed.

Reacciones adversas a L-asparaginasa en pacientes con leucemia linfoblástica aguda / Adverse reactions to L-asparaginase in children with acute lymphatic leukemia

Background: The low notification of Adverse Drug Reactions (ADR) underscores the need for pharmacological surveillance systems that allow their detection, evaluation, prevention and registry especially in patients receiving multiple medications. Aim: To communicate the ADR observed with the use E coli asparaginase (E coli ASP) in children with Acute Lymphatic Leukemia (ALL). Patients and Methods: Cross-sectional study of clinical records of all the patients aged less than 15 years with ALL (n =52) and treated between January 1996 and April 2000. The suspicion of ADR to E coli ASP was evaluated using the Karch and Lasagna algorithm. Probable and definitive cases of ADR to E coli ASP were subjected to a protocol of clinical and epidemiological data. The risk factors associated to ADR to E coli ASP, were also determined. Results: Fifty children aged 1 to 13 years (33 men) were studied. In 20 (40 percent), an ADR to E coli ASP, was suspected. After the use of the algorithm, the ADR was considered definite in two patients, probable in 17 and possible in one. The registered clinical events were urticaria in 17, anaphylactic shock in four, transient alterations of hepatic functions test in seven and hypofibrinogenemia in four. The test of cutaneous sensitivity to the administration of E coli ASP, performed prior to the administration of the drug, were positive in nine of the 20 children with adverse reactions. No children died. Conclusions: The application of the Karch anbd Lasagna algorithm, allowed us to objectively classify suspected cases of ADR by E coli ASP.