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.

 

Presenter: Dr Klaus Metzeler

 

Affiliation: (Internal Medicine 3, University Hospital, Ludwig-Maximilians-Universität (LMU) München, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany)

 

Topic: PERSISTENCE OF DRIVER MUTATIONS DURING COMPLETE REMISSION ASSOCIATES WITH SHORTER SURVIVAL AND CONTRIBUTES TO THE INFERIOR OUTCOMES OF ELDERLY PATIENTS WITH ACUTE MYELOID LEUKEMIA

Abstract S146 will be presented by Maja Rothenberg-Thurley on Friday, June 10, 2016, 16:00 - 16:10 in Hall A1.

 

About the EHA Annual Congress

Hematology is a specialty that covers everything to do with blood: its origin in the bone marrow, diseases of blood and their treatments. The latest data on research and developments will be presented. The topics range from stem cell physiology and development, to leukemia, lymphoma, myeloma - diagnosis and treatment; red blood cells -, white blood cells- and platelet disorders; thrombosis and bleeding disorders.

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Last Updated on Tuesday 05 June 2018.