A new study led by researchers at The Ohio State University Comprehensive Cancer Center–James Cancer Hospital and Solove Research Institute (OSUCCC–James) has identified combinations of gene mutations that predict whether an older person with acute myeloid leukemia (AML) might achieve complete remission when treated with standard chemotherapy.

The researchers analyzed the AML cells of 423 patients age 60 and older for mutations in 80 cancer- or leukemia-associated genes. They then used that mutation information to classify the patients into groups that had a good, poor, or intermediate outcome after treatment with standard chemotherapy.

Overall, the study, published in the journal Leukemia, highlighted the extremely poor outcome of AML patients aged 60 years and older with current treatment approaches. However, the authors found specific mutation combinations that associated with patient survival, some of which were different than those known to be associated with outcome in younger AML patients.

“This study is important,” said study leader Clara D. Bloomfield, MD, Distinguished University Professor and Ohio State University Cancer Scholar and Senior Adviser and the William Greenville Pace III Endowed Chair in Cancer Research, “because the majority of research in AML is done in patients under age 60, even though the majority of AML patients are of older age.” Bloomfield also noted that the findings might refine the classification of older AML patients who are to be treated with chemotherapy.

“We found that the number and types of chromosome changes and gene mutations are different in older AML patients compared with younger patients, along with the significance of some of those abnormalities,” Bloomfield says. “So it’s important that we evaluate older AML patients separately from younger patients.”

First author and OSUCCC–James researcher Ann-Kathrin Eisfeld, MD, a member of Ohio State’s Internal Medicine/Physician-Scientist Training Program, noted that the favorable complete response rate of the good-risk group did not lead to better overall survival, however.

Of patients in the good-risk group, 82% experienced relapse of their disease, as did patients in the intermediate-risk group. “And those groups did only slightly better than the poor-risk group, where 93% of patients relapsed,” Eisfeld says. “This tells us that once patients are in remission, they probably require additional or different treatment than chemotherapy alone to extend remission or potentially cure those patients.”

Among other findings, they showed that the “good-risk” group of patients was not only driven by the beneficial influence of NPM1 mutations, but was additionally altered by co-existing mutations in other genes.

“Our findings suggest that older AML patients should be tested for additional gene mutations before receiving standard chemotherapy,” Eisfeld says.