The treatment of pediatric leukemia has improved greatly, lowering both mortality and morbidity rates. However, these therapies are far from perfect; long-term complications and therapy failures occur in large rates, particularly among childhood survivors of acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML). As new therapies emerge, it is important to establish new standards of therapy to improve outcomes.

The investigators published a review in OncoTargets and Therapy providing an overview of previously established and new therapies in the treatment of pediatric leukemia. Currently, the 2 main approaches are systemic and targeted therapies. 

Nontargeted therapies and systemic treatments include chemotherapy, de novo liposomal agents, interferons and interleukins, and donor lymphocyte infusions (DLI).

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Chemotherapy agents such as clofarabine (Clolar in the United States, Evoltra in the European Union) and nelarabine (Arranon) have been used as single agents and demonstrate cure rates of approximately 30% in patients with ALL. Asparaginase Erwinia chrysanthemi (Erwinaze) was recently approved for the treatment of ALL in patients who develop Escherichia coli-derived asparaginase hypersensitivity.

De novo liposomal agents are used as highly effective vehicles in delivering chemotherapy to cancer cells, minimizing systemic adverse effects. Standard agents currently used in treatment regimens for childhood leukemia include liposomal vincristine sulfate (Marqibo), sustained-release DepoFoam cytarabine (DepoCyte), liposomal formulation DNR (DaunoXome), liposomal formation doxorubicin (Myocet), and pegaspargase (PEG-L-asparaginase; Oncospar). L-annamycin (Annamycin) is currently being evaluated for use in both pediatric and adult relapsed or refractory AML.

Interferons and interleukins behave as nonspecific immunotherapies, and have a multitude of effects. They are able to resist cancers and infections, block cancer cell growth, stimulate innate immune defenses, and also augment the effects of chemotherapy. They are used in the treatment of non-Hodgkin lymphoma (NHL), cutaneous T-cell lymphoma, chronic myeloid leukemia, and hairy cell leukemia. A novel formulation is pegylated-IFN-alpha (Pegasys). 

In DLI, patients receive allogeneic stem cell transplants from a donor. Newer strategies such as infusing donor-derived, ex vivo-expanded CD8(+) cytotoxic T lymphocytes, and granulocyte-colony stimulating factor (GCSF)-mobilized peripheral blood progenitor cells, and allo-depleted donor T-cells as DLI have led to better outcomes.

Targeted therapies include enzyme inhibitors, cluster of designation (CD) antibodies, immunotherapy, radio immunotherapy, and small molecules.

Enzyme inhibitors specifically inhibit gene rearrangements and actionable protein products. Tyrosine kinase inhibitors such as imatinib (Gleevec), dasatinib (Sprycel), and nilotinib (Tasigna) are currently used to treat ALL. FLT-3 inhibitors such as lestaurtinib (Hydrate) are used in patients with MLL-rearranged ALL. Forodesinne (Mundesine) is a purine nucleoside phosphorylase inhibitor for ALL. Decitabine (Dacogen), a DNA methyltransferase inhibitor, and vorinostat (Zolinza), a histone deacetylase inhibitor, are currently being evaluated as potential treatments for ALL.