Persistence of preleukemic clones in acute myeloid leukemia (AML) complete remission

Klaus Metzeler, MD, from the University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany, describes his talk on the persistence of mutations in preleukemic clones during complete remission (CR) in acute myeloid leukemia (AML) at the International Symposium on Acute Leukemias (ISAL) 2017 in Munich, Germany. He explains that preleukemic clones are a group of cells that have some mutations that leukemia has, but which are still capable of normal differentiation. If AML is treated with chemotherapy and the patient goes into remission, these preleukemic clones can persist in the bone marrow and make up a substantial amount of hematopoiesis in remission. Dr Metzeler investigated whether these preleukemic clones are associated with clinical characteristics and treatment outcomes by looking at driver mutations in leukemia diagnosis and determining whether these mutations are still found when the patient is in remission. He explains that in around 40% of patients, some mutations are still found in morphologically normal remission bone marrow. These patients had a higher rate of relapse and decreased overall survival (OS) than those who cleared all mutations. In general, the patients with persisting preleukemic clones are older than those who clear all mutations, which is interesting as in apparently healthy older people there is also a high incidence of clonal hematopoiesis. He concludes that leukemias from preleukemic clones may be biologically distinct and more difficult to treat. Regarding treatment options for patients with persisting clones, Dr Metzeler explains that those who do not receive an allogenic stem cell transplant have a high rate of relapse, while those who do receive a transplant have a lower relapse rate. He suggests that the detection of preleukemic clones in remission may be a tentative indication that an allogenic stem cell transplant should be given if the patient is able to receive this. However, because many of these patients are older, some may not be fit enough to receive transplants, and so new strategies to eradicate persistent clones are required.

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