Novel approaches to pediatric leukemia treatment

Abstract

Despite remarkable improvements in the treatment of pediatric acute leukemia (AL) over the last decades, relapse still carries a poor prognosis with significant morbidity and mortality. Novel targeted therapies are currently being investigated in an attempt to reduce adverse events and improve survival outcomes. This review summarizes recent data from the literature regarding advances in drug discovery based on biological evidence and the novel targeted drug therapies for childhood AL. Significant challenges still remain for novel drug development in childhood AL. However, first results combined with a large number of new agents currently being investigated are very encouraging. Furthermore, therapeutic advances will depend upon combination strategies using the specific action of each agent and their complementary effects on leukemia cells.

Keywords:

• acute leukemia
• children
• drug discovery
• prognosis
• targeted therapy

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Key issues

• Although major advances have been made with standard chemotherapy in the treatment of childhood acute leukemia (AL), additional gains are unlikely to be achieved by simply intensifying therapy further, while encouraging signs have been shown with the development of novel targeted therapies.

• Among new agents, antibody therapy, used alone or incorporated into standard chemotherapy backbones, represents one of the most exciting novel therapeutic approaches for AL.

• T cells genetically modified to express chimeric antigen receptors, which recognize specific targets on leukemic cells, are expected to revolutionize our way to fight against AL, by redirecting the immune system in order to eliminate relapse issues.

• Imatinib mesylate and the other inhibitors of the Abelson tyrosine kinase activity of the fusion protein breakpoint cluster region-Abelson have revolutionized the treatment of Philadelphia chromosome-positive acute lymphocytic leukemia and have been shown to be highly effective in children.

• In a near future, patients will need to be treated with a combination of therapeutic agents, in which each agent would be expected to be effective in a subset of molecular abnormality involved in the leukemic process.