Pharmacogenetics in Childhood Acute Lymphoblastic Leukemia

Primary genetic abnormalities of leukemic cells are well recognized to have important prognostic and therapeutic significance.1 Host factors can also influence treatment efficacy.2,3 For example, given the same dosages of mercaptopurine or methotrexate, reduced accumulation of active metabolites in leukemia cells, due to fast clearance, inactivation, or other reasons, has been associated with a poor outcome in acute lymphoblastic leukemia (ALL).4 The concomitant administration of certain anticonvulsants (e.g., phenytoin, phenobarbital, or carbamazepine) increases the systemic clearance of antileukemic agents by inducing the production of cytochrome P-450 enzymes, and therefore leads to poor treatment outcome of ALL.5 Conversely, azole antifungal agents inhibit these enzymes, thereby increasing the efficacy or toxicity of chemotherapy such as vincristine.1

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