Relapse in leukemia tied to mutations that persist through treatment

26 Aug

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.

DNA magnifying glass
The study shows mutations that persist through chemotherapy are linked to relapse and poor survival in patients with acute myeloid leukemia.

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


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


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

Copyright: Medical News Today

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