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University of Florida researchers have developed a new genomics-based score to deliver more personalized and effective chemotherapy treatments to pediatric leukemia patients.

The predictive score brings a precision medicine approach to treating childhood acute myeloid leukemia, or AML, a common form of childhood leukemia.

AML spreads rapidly and affects the bone marrow and blood. The chemotherapy drug cytarabine has been a mainstay of AML treatment for more than 50 years. However, it fails to induce remission in about 10-15% of children, and another 40% will relapse after achieving remission.

In a study published in the , one of the top journals in the field, UF researchers outlined how they developed a patient-specific polygenic score to improve treatment outcomes. The score was generated by performing a comprehensive pharmacogenomic evaluation of cytarabine鈥檚 drug pathway in the body and predicting how much of the drug is activated in a cell.

鈥淐ytarabine must be activated to effectively kill leukemia cells, but the amount of activation varies based on an individual鈥檚 genetics,鈥� said , Ph.D., M.Sc., the study鈥檚 lead author and a professor of , a part of 网红黑料, the university鈥檚 academic health center. 鈥淲e anticipated our score would predict the outcome 鈥� and it did 鈥� but what was really interesting is that we were able to show if the patient had a low, or detrimental score, the outcome could be improved by augmenting the patient鈥檚 therapy.鈥�

The study included more than 1,000 pediatric cancer patients treated through multisite clinical trials at St. Jude Children鈥檚 Research Hospital and the Children鈥檚 Oncology Group. It suggested patients with a low polygenic score would benefit from increased dosing of cytarabine or additional targeted therapies in their chemotherapy regimen. Meanwhile, patients with a high score may benefit from a less-intensive chemotherapy regimen 鈥� avoiding some of the toxicity associated with cytarabine.

鈥淲ith this score, we can genetically define those patients who would benefit from intensifying the chemotherapy or adding a new cancer drug to the regimen and on the other side of the spectrum having their chemotherapy reduced to avoid toxicity,鈥� Lamba said. 鈥淭he score gives clinicians a new tool to devise an effective treatment strategy and deliver the best possible outcome to AML patients. It also has the potential to improve the guidelines for delivering AML chemotherapy.鈥�

Another key finding in the study involved the role race and ethnicity play in generating the predictive score. UF researchers found the high score significantly differed by race, with 70% of white patients and only 30% of Black patients having a beneficial score. The study鈥檚 results suggest the polygenic score could be one of the underlying contributors to observed racial disparities in AML patient outcomes and may have the potential to reduce the observed racial disparities by optimizing treatment.

Lamba, the Frank A. Duckworth Eminent Scholar Chair in the and a member of the , said further exploration is needed to determine whether Black patients would benefit from a higher dose of cytarabine or additional drugs in their chemotherapy regimen.

鈥淭his study opens opportunities for examining how race and ethnicity impact AML patient response to cancer treatments,鈥� Lamba said. 鈥淲e need to be more conscious of racial disparities in cancer care and continue to investigate why we are seeing different outcomes by race.鈥�

Lamba has joined a consortium of researchers in Africa studying racial disparities in cancer treatment. She expects the collaboration will create new opportunities for studying drug response in Black patients and allow for further research involving the new scoring model.

鈥淒r. Lamba鈥檚 innovative research program explores hidden genetic complexity behind response to therapy and serves as a cautionary lesson to all cancer researchers to enroll robust numbers of diverse individuals in clinical trials, in order to elucidate and address disparities,鈥� said , M.D., director of the 网红黑料 Cancer Center. 鈥淭his is a theme embraced across all 网红黑料 Cancer Center research programs.鈥�

The study 鈥�,鈥� was published Jan. 6 in the Journal of Clinical Oncology, a peer-reviewed medical journal published by the American Society of Clinical Oncology. Multiple investigators from St. Jude Children鈥檚 Research Hospital, the Children鈥檚 Oncology Group, Tennessee 网红黑料 Sciences Center, Fred Hutchinson Cancer Research Center, Children鈥檚 Mercy Hospital, Nemours Children鈥檚 网红黑料 and the University of Florida contributed to the study.

Media contact: Ken Garcia at kdgarcia@ufl.edu or 352-273-9799.