Relapse in leukemia tied to mutations that persist through treatment

Acute myeloid leukemia patients with mutations that linger through chemotherapy have a higher risk of relapse and lower rates of survival than patients whose mutations are cleared by the treatment.


This was the key finding of a study led by the Washington University School of Medicine, in St Louis, MO, that was published in JAMA.

The finding suggests doctors should run genetic tests to look for the persistent mutations once chemotherapy has finished so that decisions about whether to start more aggressive treatments can be made early during remission.

Senior author Timothy J. Ley, a professor of oncology, says most patients diagnosed with acute myeloid leukemia (AML) "fall into a gray area" when doctors try to predict their risk of relapse.
"About 80% of AML patients go into remission with chemotherapy, but most of them eventually will relapse," he adds. "Unfortunately, we still don't have a definitive test that tells us early on which patients will relapse."

AML is the deadliest form of leukemia. It is an uncommon cancer that rarely strikes before the age of 45. The average age of a patient with AML is about 67 years. The disease causes overproduction of myeloblasts or leukemic blasts (immature white blood cells) that crowd the bone marrow and stop it from producing normal blood cells.

The American Cancer Society estimates that in 2015, there will be around 54,270 new cases of leukemia in the US, of which about 20,830 will be AML, mostly in adults. Around 24,450 Americans will die of leukemia, including 10,460 from AML (nearly all adults).

For their study, Prof. Ley and colleagues ran genetic profiles of bone marrow samples from AML patients. They found those whose cells still had mutations 30 days after starting chemotherapy treatment were around three times more likely to relapse and die than patients whose cells were cleared of them.

Prof. Ley says it is important to know which patients have persistent mutations because they will need aggressive - yet potentially curative - therapy such as stem-cell transplant while they are in remission.
Doctors do not want to put patients through such an aggressive, expensive and risky procedure with potentially severe side effects if they are unlikely to relapse following conventional chemotherapy, he adds.

Findings need to be confirmed by larger studies

The researchers note that their study was retrospective - they looked at bone marrow samples from patients whose outcomes were already known.
They sequenced samples taken from 71 AML patients at time of diagnosis, and also from another 50 patients whose samples were taken at time of diagnosis and also 30 days after chemotherapy.
Mutations in the samples taken at time of diagnosis did not help to predict risk of relapse after chemotherapy any better than standard methods.

However, mutations that persisted through chemotherapy - those that were present before chemotherapy and found to be still present 30 days after treatment started - were linked to poor survival.

A total of 24 of the 50 patients whose samples were taken at diagnosis and after chemotherapy had persistent mutations and their median survival was 10.5 months, compared with 42 months for the 26 patients without persistent mutations.

The researchers say their findings now need to be confirmed by larger studies. If they are, they suggest genetic profiling after initial chemotherapy could improve early prognosis and help decide whether chemotherapy has worked before the cancer recurs. Prof. Ley concludes:

"This new approach gives us a way to think about how to use genomics to evaluate the risk of relapse for nearly all AML patients."

He and his colleagues also suggest the findings could be useful for other cancers.

Earlier this year, Medical News Today reported on a study by researchers in Canada that suggests a compound found in avocados shows promise as a leukemia treatment. The study shows that the compound, avocatin B, selectively destroys leukemia stem cells without harming healthy cells.
Written by Catharine Paddock PhD