Terapias emergentes y farmacogenética en la leucemia linfoblástica aguda pediátrica: revisión narrativa crítica con enfoque traslacional

Sebastián Arguedas Chacón
Departamento de Investigación, Hospital Clínica Bíblica, San José, Costa Rica.

Mauricio Villegas Campos
Investigador Independiente, San José, Costa Rica.

Resumen

La leucemia linfoblástica aguda (LLA) es el cáncer más frecuente en la edad pediátrica y, pese a los notables avances terapéuticos, un subgrupo de pacientes continúa presentando recaídas, toxicidad significativa y mortalidad asociada al tratamiento. En las últimas dos décadas, la incorporación de terapias dirigidas, inmunoterapia y herramientas de farmacogenética ha transformado el abordaje clínico de esta enfermedad. Sin embargo, la magnitud real de su impacto clínico, particularmente sobre la supervivencia global y libre de eventos en pacientes de alto riesgo, sigue siendo motivo de debate.  

Esta revisión narrativa crítica analiza de forma integrada la evidencia disponible sobre terapias emergentes e implementación de la farmacogenética en LLA pediátrica, con especial énfasis en su aplicabilidad clínica real. Se revisan las terapias dirigidas actualmente utilizadas o en investigación, así como los principales biomarcadores farmacogenéticos implicados en la respuesta y toxicidad al tratamiento. Se discuten los beneficios consolidados en términos de reducción de toxicidad y optimización de la tolerancia terapéutica, junto con las limitaciones metodológicas que explican la ausencia de evidencia robusta de mejora en supervivencia, especialmente en enfermedad de alto riesgo. Finalmente, se plantean retos y oportunidades para la integración de una medicina personalizada traslacional en la práctica clínica pediátrica.

Palabras claves

Leucemia linfoblástica aguda, pediatría, farmacogenética, medicina de precisión.

Abstract

Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood, and despite remarkable therapeutic advances, a subset of patients continues to experience relapse, significant toxicity, and treatment-related mortality. Over the past two decades, the incorporation of targeted therapies, immunotherapy, and pharmacogenetic tools has transformed the clinical management of this disease. However, the true magnitude of their clinical impact, particularly on overall survival and event-free survival in high-risk patients, remains a matter of debate.

This critical narrative review integrates the available evidence on emerging therapies and the implementation of pharmacogenetics in pediatric ALL, with special emphasis on real-world clinical applicability. Currently used and investigational targeted therapies are reviewed, along with the main pharmacogenetic biomarkers involved in treatment response and toxicity. Established benefits in toxicity reduction and optimization of treatment tolerability are discussed, together with the methodological limitations that explain the lack of robust evidence for improved survival, especially in high-risk disease. Finally, challenges and opportunities for integrating translational personalized medicine into pediatric clinical practice are outlined.

Keywords

Acute lymphoblastic leukemia, pediatrics, pharmacogenetics, precision medicine.

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