In addition to tumor genetic, the i

In addition to tumor genetic, the individual genetic variability is important in the delivery of the most efficacious treatment plan. Germ line polymorphisms, in genes of drug-metabolizing enzymes, transporters, receptors, and drug targets, can greatly affect the individual’s response to therapy. It is estimated that germ line polymorphisms in genes involved in antileukemia drug metabolism are common, with the frequency of the variant allele ranging from 5% to 50%
Several germ line polymorphisms have been found to significantly affect the metabolism of antileukemia therapy, potential toxicity, and event free survival. For example, a well-documented polymorphism of the enzyme thiopurine methyl transferase(TPMT), responsible for the inactivation of mercaptopurine, results in prolonged 6-mercaptopurine exposure resulting in an increased risk of bone marrow toxicity. It is recommended that all children undergoing ALL, if present, that the dise of 6-mercaptopurine be adjusted to prevent bone marrow toxicity. Due to drug sensitivity, the TPMT polymorphism has been associated with a low ALL relapse rates.
Other individual considerations are concurrent medications during the course of therapy. It is known that particular seizure medications such as phenytoin, Phenobarbital, or carbamazepine induce the cytochrome P-450 enzymes and increase the clearance of chemotherapy agents with less leukemia exposure to the therapeutic agent. Therefore, it is imperative that the initial assessment consider the pharmacological mechanism of concurrent medications and their effect on chemotherapy metabolism and clearance.