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EHA 2016: Pre-leukaemic clones that survive chemotherapy are linked to a higher risk of AML recurrence

10 Jun 2016
EHA 2016: Pre-leukaemic clones that survive chemotherapy are linked to a higher risk of AML recurrence

Acute myeloid leukaemia (AML) is an aggressive form of blood cancer.

Treatment with intensive chemotherapy often leads to a period of freedom from overt disease called a remission.

However, recurrence of the disease is common.

For reasons that are not yet fully understood, older patients have a higher risk of relapse.

In some patients, AML originates from a clone of pre-leukaemic stem cells.

These pre-leukaemic stem cells already carry genetic changes (mutations) that are also found in leukaemias, but they still can give rise to normal-appearing blood cells.

The subsequent gain of additional mutations then causes progression to overt AML.

When the AML clone is eradicated by chemotherapy, a pre-leukaemic clone remains detectable in some patients.

We therefore studied sample pairs collected at the time of leukaemia diagnosis, and after chemotherapy while the patient was in remission, from 107 patients with AML.

In 36% of these patients, some of the gene mutations found in the leukaemia were still present in the remission specimen, indicating the persistence of a pre-leukaemic clone.

Persisting mutations were more frequent in older patients.

Importantly, patients with persisting mutations had a higher risk of subsequent disease recurrence compared to those with no persisting mutation.

Multivariate statistical analyses, which also take other known risk factors into account, suggest that the higher incidence of persisting pre-leukaemic clones in older patients may be one explanation for the higher risk of AML relapse in this age group.

Source: EHA