Different Leukemia, Different Treatment

Acute myeloid leukemia mutations treated with high dose daunorubicin

(RxWiki News) Many genetic changes are involved in any given cancer, but some changes are very important to consider for chemotherapy. Acute Myeloid Leukemia (AML) is an example of a cancer where treatment can vary widely depending on the genetics involved.

Data published in a recent study by the Eastern Cooperative Oncology Group found that AML patients responded differently to chemotherapy depending on their age group. A team from H. Lee Moffitt Cancer Center & Research Institute reviewed the results from that first study and hypothesized that the age difference reflected an underlying genetic difference.

"Ask your oncologist if your leukemia would benefit from high-dose chemotherapy."

The Moffitt Cancer Center team took frozen samples from the earlier study and performed genetic sequencing on the cancer samples. After analyzing for mutations in 18 genes in each of the 398 patients, they concluded that mutations in the genes DNMT3A, NPM1, and MLL belonged to the group that responded well to high dose daunorubicin, a chemotherapy agent.

The researchers found that patients with mutations in these three genes had the best treatment success if given high dose chemotherapy.

Using their data from the first study, the team tested the genetic mutation theory in a second experiment with 104 patients. They found that the results held up as projected and discovered that patients without those specific mutations were not helped by high dose chemotherapy.

Study co-author, Hugo F. Fernandez, M.D., a senior member at Moffitt, spoke about the results. "Recent studies have revealed that a number of genetic mutations in AML patients might have prognostic value. The question of the presence of these gene mutations altering outcomes based on current therapy had not been answered to date."

Dr. Fernandez went on to say that increasing dosing in patients with these mutations significantly impacted outcomes and improved survival. 

"Most importantly," said Dr. Fernandez, "this study demonstrates how integrated mutational profiling of samples from a clinical trial cohort can advance understanding of the biologic characteristics of AML."

Results were published online in March 22's edition of the New England Journal of Medicine.

Research was funded by the National Cancer Institute, Gabrielle's Angel Fund, Starr Cancer Consortium, Peter Solomon Fund, American Society of Hematology, the Leukemia and Lymphoma Society, Sackler Center for Biomedical and Physical Sciences, and the Howard Hughes Medical Institute.

Review Date: 
March 28, 2012