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  • Clinical Implications
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Clinical Implication

Pharmacogenomic effects on therapy for acute lymphoblastic leukemia in children

The Pharmacogenomics Journal volume 3, pages 128–135 (2003)Cite this article

Acute leukemias account for approximately one-third of all childhood cancers worldwide. Acute lymphoblastic leukemia (ALL) is the most common cancer in children, with about 2500 new cases diagnosed in the United States each year. Since the introduction of systemic chemotherapy, cure rates for childhood ALL have improved from less than 10% in the 1960s to 80% today.1 Individual response to therapy depends on multiple factors, including biologic and genetic features of the leukemia blasts at the time of diagnosis, as well as characteristics of the patient. In addition, tumor cells have the ability to rapidly incorporate phenotaypic changes that render them resistant to an array of structurally diverse chemotherapeutic agents. Multiple studies have found wide interpatient variability in overall exposure to drugs and tolerability of drug regimens for ALL. Therefore, relapse may be attributed to drug resistance of leukemic cells or to inadequate drug exposure as a result of interpatient variability in pharmacokinetics. A large body of research now focuses on the 20% of patients who are not cured with upfront therapy, and seeks to define genetic differences in either somatic or tumor cells that are associated with treatment failure.

Children with ALL, who are cured by upfront therapy, are anticipated to have a long life expectancy. As improvements in drug therapy lead to more cures, investigators seek ways to minimize host toxicity (both acute and chronic side effects) while continuing to achieve excellent cure rates. Recent studies suggest that baseline genetic characteristics of the host may predict chronic toxicity as well as acute toxicity. As microarray technologies become more widely available, it may be possible to detect these genetic variations prior to therapy and maximize future quality of life for these children.

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Acknowledgements

We thank Evan Katz for generating the artistic depictions of the figures and Julia Cay Jones for expert editorial review. This work was supported in part by the Cancer Center Support Grant CA21765 from the National Cancer Institute and by the American Lebanese Syrian Associated Charities (ALSAC).

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Authors and Affiliations

  1. Division of Clinical Pharmacology and Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA

    A M Wall

  2. Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA

    J E Rubnitz

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Correspondence to J E Rubnitz.

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Wall, A., Rubnitz, J. Pharmacogenomic effects on therapy for acute lymphoblastic leukemia in children. Pharmacogenomics J 3, 128–135 (2003). https://doi.org/10.1038/sj.tpj.6500174

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