ABSTRACT
La L-asparraginasa (L-ASP) es una de las piedras angulares del tratamiento de la leucemia linfoblástica aguda y del linfoma no Hodgkin. Es una enzima de origen bacteriano con capacidad de transformar la L-Asparragina en ácido aspártico; la depleción extracelular de este aminoácido inhibe la síntesis proteica en los linfoblastos induciendo su apoptosis. Numerosos estudios han demostrado que los tratamientos con L-ASP mejoran la supervivencia de estos pacientes, pero existen diferencias en las características de las 3 formulaciones disponibles en la actualidad. Este artículo revisa la dosificación, actividad y efectos secundarios de las 2 L-ASP derivadas de Escherichia coli (la nativa y la pegilada) y de la única derivada de Erwinia chrysanthemi (Erwinia ASP). A pesar de su indiscutible indicación en los últimos 50 años, siguen existiendo numerosos puntos de controversia, y su uso todavía sigue marcado por los efectos secundarios derivados de la inhibición de la síntesis proteica. La vida media corta de las formas nativas y la vía de administración intramuscular, la más utilizada hasta el momento, afecta la calidad de vida de estos pacientes por la frecuencia con la que han de acudir al centro hospitalario y las múltiples punciones que conlleva. Por ello, los estudios más recientes pretenden valorar otras alternativas como la formulación de vida media más larga (L-ASP pegilada) y la vía intravenosa, con resultados alentadores. Aun así, son necesarios más estudios para establecer cuál es la formulación y la vía de administración indicada en primera línea, la dosificación óptima y el manejo de los efectos adversos (AU)
L-asparaginase (L-ASP) is one of the cornerstones of the treatment of acute lymphoblastic leukemia and non-Hodgkin lymphoma. It is an enzyme of bacterial origin capable of transforming L-asparagine to aspartic acid. The extracellular depletion of L-asparagine inhibits protein synthesis in lymphoblasts, inducing their apoptosis. Numerous studies have demonstrated that treatment with L-ASP improves survival of patients, but there are clear differences in the characteristics of the three currently available formulations. This article reviews the dosage, activity and side effects of the two L-ASP derived from Escherichia coli (native and pegylated), and the one derived from Erwinia chrysanthemi (Erwinia ASP). Despite its indisputable indication over the past50 years, there are still many points of contention, and its use is still marked by the side effects of the inhibition of protein synthesis. The short half-life of native forms, and the most frequently used parenteral administration by intramuscular injections, affects the quality of life of the patients. Therefore, recent studies claim to evaluate alternatives, such as the formulation of longer half-life pegylated L-ASP, and the use of intravenous formulations. There are encouraging results to date with both preparations. Still, further studies are needed to establish which should be the formulation and frontline indicated route of administration, optimal dosing, and management of adverse effects (AU)
Subject(s)
Humans , Male , Female , Child , Asparaginase/therapeutic use , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Hodgkin Disease/drug therapy , Molecular Targeted Therapy/methods , Antineoplastic Agents/therapeutic use , Pancreatitis/chemically induced , Chemical and Drug Induced Liver InjuryABSTRACT
L-asparaginase (L-ASP) is one of the cornerstones of the treatment of acute lymphoblastic leukemia and non-Hodgkin lymphoma. It is an enzyme of bacterial origin capable of transforming L-asparagine to aspartic acid. The extracellular depletion of L-asparagine inhibits protein synthesis in lymphoblasts, inducing their apoptosis. Numerous studies have demonstrated that treatment with L-ASP improves survival of patients, but there are clear differences in the characteristics of the three currently available formulations. This article reviews the dosage, activity and side effects of the two L-ASP derived from Escherichia coli (native and pegylated), and the one derived from Erwinia chrysanthemi (Erwinia ASP). Despite its indisputable indication over the past50 years, there are still many points of contention, and its use is still marked by the side effects of the inhibition of protein synthesis. The short half-life of native forms, and the most frequently used parenteral administration by intramuscular injections, affects the quality of life of the patients. Therefore, recent studies claim to evaluate alternatives, such as the formulation of longer half-life pegylated L-ASP, and the use of intravenous formulations. There are encouraging results to date with both preparations. Still, further studies are needed to establish which should be the formulation and frontline indicated route of administration, optimal dosing, and management of adverse effects.
Subject(s)
Antineoplastic Agents/therapeutic use , Asparaginase/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Child , HumansSubject(s)
Female , Male , Infant , Humans , Leukemia, Myelomonocytic, Juvenile/complications , Leukemia, Myelomonocytic, Juvenile/pathology , Splenomegaly/complications , Granulocyte Precursor Cells/cytology , Biopsy, Needle/methods , Bone Marrow/anatomy & histology , Fetal Hemoglobin/adverse effectsABSTRACT
Autoimmune hemolytic anemia (AIHI) is an infrequent disease in the pediatric age group. Its diagnosis is given by the direct antiglobulin test (DAT) or Coombs' test, which determines which type of globulin (IgG or complement) is the cause of the hemolysis. The type of globulin involved determines the etiology of AIHI, which is usually confirmed by positive results of other laboratory investigations such as cold agglutinin determination or the Donath-Landsteiner test. We present three cases of AIHI. DAT was positive to complement with diverse etiology: warm antibody with IgG-negative DAT, cold agglutinins associated with infectious mononucleosis, and Doth-Landsteiner antibodies. In all patients, empirical treatment with corticosteroids was initiated. The treatment was withdrawn or continued, depending on the final etiology of AIHI.
Subject(s)
Anemia, Hemolytic, Congenital , Antibodies, Anti-Idiotypic/metabolism , Autoimmune Diseases/immunology , Coombs Test/methods , Immunoglobulin G/immunology , Adolescent , Anemia, Hemolytic, Congenital/diagnosis , Anemia, Hemolytic, Congenital/immunology , Anemia, Hemolytic, Congenital/metabolism , Child, Preschool , Female , Humans , MaleABSTRACT
La anemia hemolítica autoinmune (AHAI) es una enfermedad poco frecuente en la edad pediátrica. Su diagnóstico se establece mediante la prueba de antiglobulina directa (PAD) o test de Coombs que determina qué tipo de globulina (IgG o complemento) es la causante de la hemólisis. Dependiendo del tipo de globulina que resulte, ésta orienta la etiología de la AHAI, que se suele confirmar a través de la positividad de otras pruebas de laboratorio, como la determinación de crioaglutininas o la prueba de Donath-Landsteiner. Se presentan 3 casos de anemia hemolítica autoinmune con PAD positiva a complemento con etiología diferente: por anticuerpos calientes con PAD negativa a IgG, por crioaglutininas asociadas a mononucleosis infecciosa y por anticuerpos de Donath-Landsteiner. En todos los casos se inició tratamiento empírico con corticoides que se suspendió o continuó según la etiología final de la AHAI. (AU)
