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The root of evil: Pre-leukemic clones that survive chemotherapy are linked to a higher risk of leukemia recurrence

Acute myeloid leukemia (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-leukemic stem cells.

These pre-leukemic stem cells already carry genetic changes (mutations) that are also found in leukemias, 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-leukemic clone remains detectable in some patients. We therefore studied sample pairs collected at the time of leukemia 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 leukemia were still present in the remission specimen, indicating the persistence of a pre-leukemic 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-leukemic clones in older patients may be one explanation for the higher risk of AML relapse in this age group.

Abstract S146: Persistence of Driver Mutations During Complete Remission Associates with Shorter Survival and Contributes to the Inferior Outcomes of Elderly Patients with Acute Myeloid Leukemia, EHA Annual Congress.