Defining differences

Key Points

One size doesn't fit all. Whether it's the fit of a T-shirt or a patient's reaction to a medication, there is often no universal solution. No one understands individual differences better than Mary Relling, PharmD, who has devoted her career to finding better treatment options for childhood leukemia patients based on their genetic differences.

These researches drew the attention of the Pediatric Pharmacy Advocacy Group, which recently honored Relling with the Sumner J. Yaffe Lifetime Award in Pediatric Pharmacology and Therapeutics.

The award is the latest in a succession of accolades Relling has received for her work over the course of a career that has allowed her to combine her 2 passions: oncology research and pediatrics.

This is the path she has wanted to take since she was a resident pursuing her Doctor of Pharmacy degree at the University of Utah in the 1980s.

"I was having a hard time deciding between pediatrics and oncology, and somebody said, well, why don't you do both," she said.

The result has been a successful career at St. Jude Children's Research Hospital, where Relling has been able to focus on childhood acute lymphoblastic leukemia (ALL).

Genetic variability

The disease has been a good model for pharmacogenetic research, said Relling, because it is largely curable with medications alone.

However, often that means that patients are given anywhere from 6 to 10 different anticancer drugs at a time, drugs that they may have to take for as long as 3 years.

Common medications for treating ALL, such as methotrexate, mercaptopurine, asparaginase, dexamethasone, and etoposide are often also associated with serious adverse effects.

Relling and her team are working to find ways to individualize drug therapy that will decrease the adverse effects that patients experience without diminishing the antileukemic effects of the drugs.

"Genetic variability is a lot of the reason that patients differ from each other pharmacokinetically and pharmacodynamically," she said. "Pharmacogenomics is one of the tools that we can use to explain why the same medications that work terrifically in some patients don't work well in others."

Tests for subgroups

One aspect of Relling's research seeks to determine whether certain subgroups of patients would benefit from genetic testing more than others.

According to Relling, who has published more than 200 peer-reviewed articles and who also serves as a professor at the University of Tennessee Health Science Colleges of Pharmacy and Medicine, treatment decisions for most patients may be made on the basis of conventional risk factors such as age, presenting white blood cell count, and kidney and liver function.

However, certain patients may need more specific testing to determine their optimum treatment regimen.

"For example, we recently found that if you do a genome-wide screen of all kids with leukemia, those kids who have a high Native American ancestry - and in the United States that turns out to be most people who are self-declared Hispanic by ethnicity - those patients have a higher risk of relapse if we give them normal ALL chemotherapy, compared to patients that don't have a high Native American ancestry, and it's independent of other conventional risk factors," she said.