You are caring for a child with acute lymphoblastic leukemia. She has been genotyped and is homozygous for a TPMT polymorphism, producing very little of the enzymeneeded for this drug's metabolism. How would you expect this to affect dosing of the drug 6-mercaptopurine?
A)This child should receive only a small fraction of the standard dose.
B)This child should receive the drug intravenously rather than orally.
C)This child should receive higher doses than the standard dose.
D)This child should receive the standard dose.

Question

Quizplus · Accepted Answer

Drugs such as azathioprine (Imuran), mercaptopurine, and thioguanine used to treat childhood leukemias, rheumatoid arthritis, or inflammatory bowel disease require metabolism by the enzyme thiopurine methyltransferase (TPMT). The activity of TPMT is trimodal, meaning three different levels of enzyme activity exist among groups of people. About 90% of people have high TPMT activity. They have faster drug metabolism, which results in lower exposure of leukemic cells to active thiopurines. About 10% of people have intermediate activity, and a very small fraction of people (about 0.3%) have low activity. Those who have low TPMT activity are homozygous for variations in the gene coding for TPMT, so they produce nonfunctional protein. People with low TPMT activity risk myelosuppression, secondary cancers, and possibly fatal toxicity when they are given chemotherapeutic agents requiring metabolism by TPMT. They must either have the dose of their chemotherapeutic agents reduced eight- to tenfold or be placed on drugs that do not use TPMT for metabolism and elimination.

You Are Caring for a Child with Acute Lymphoblastic Leukemia