Treatment and biology of pediatric acute lymphoblastic leukemia

Abstract

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. In the past ALL was intractable but now the survival probability is as high as 80-90%. Improved supportive care, treatment stratification based on relapse risk, biological features of leukemic cells, and optimization of treatment regimens by nationwide and international collaboration have contributed to this dramatic improvement. While including traditional risk factors (e.g., age and leukocyte count at diagnosis), the treatment has been modified based on biological characteristics (aneuploidy and translocation) and treatment response (assessed by minimal residual disease). Treatment for pediatric ALL typically consists of induction therapy with steroids, vincristine, and asparaginase with or without anthracycline, followed by multiagent consolidation including high-dose methotrexate and re-induction therapy. After consolidation, less intensive maintenance therapy is required for 1-2 years to maintain event free survival of the patients. Recently, advanced genomic analysis technology identified novel sentinel genomic alterations which may provide more precise stratification or therapeutic targets. Moreover, in the last decade we have seen that germline variations are similarly important contributors to understanding the etiology and sensitivity of ALL to treatment. A more individualized approach based on genomic features (somatic and germline) and treatment response, the introduction of newly developed agents such as molecular targeted drugs or immunotherapy, and social supports including long-term follow up are required for further improvement.