The Role of Pharmacogenomics in Reducing Racial Disparities in Pediatric AML Treatment Outcomes

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A new study in JAMA Network Open suggests that disparities in outcomes between Black and White children with acute myeloid leukemia may be due to differences in pharmacogenomics, which is how genes affect drug responses.

When comparing treatment outcomes for patients with blood cancers, such as acute myeloid leukemia (AML), previous research demonstrates that racial and ethnic disparities exist.

A new study published May 16 in JAMA Network Open sheds light on a potential reason for the disparities in outcomes between Black and White children with AML.

The findings suggests that the discrepancies are related to differences in pharmacogenomics. According to MedlinePlus, pharmacogenomics is the study of how genes impact a person's response to drugs.

Pharmacogenomic researchers are studying how genetic variants affect drug response and exploring new approaches to tailor treatments for various health conditions. This growing field aims to develop personalized medications based on an individual's genetic makeup in order to improve treatment outcomes.

The study, conducted by a group of researchers including corresponding author Jeffrey E. Rubnitz, M.D., Ph.D., at St. Jude Children’s Research Hospital, aimed to assess whether tailoring the intensity of induction therapy could mitigate racial disparities in outcomes in pediatric patients with AML.

To investigate, the researchers utilized databases from two previous clinical trials: AML02, conducted from 2002 to 2008, and AML08, conducted from 2008 to 2017. Included in the new analysis were 86 Black children and 359 White children with newly diagnosed AML who participated in either trial.

Patients in the AML02 trial were randomly assigned to receive either standard low-dose cytarabine-based induction therapy or augmented high-dose cytarabine-based induction therapy. Patients who were enrolled in the AML08 trial received high-dose cytarabine-based therapy.

The main findings of the analysis revealed that Black patients who received standard induction therapy had significantly poorer outcomes compared to White patients. However, when Black patients received augmented induction therapy, there were no differences in treatment outcomes between the two groups. Additionally, the study found that the use of cytarabine pharmacogenomic 10-single-nucleotide variant (ACS10) scores played a significant role in predicting treatment outcomes.

“We propose that the high prevalence of low ACS10 scores among Black patients is also associated with the poor outcomes reported in other studies, which primarily included patients who underwent standard, low-dose cytarabine–based induction therapy in cooperative group trials,” the authors wrote in their paper.

In their conclusion, the authors wrote that future studies should look at tailoring induction regimens based on pharmacogenomic parameters to improve outcomes for Black and White pediatric patients with AML and address the racial gap in treatment outcomes.

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