Treatment of Low-Blast Count AML using Hypomethylating Agents

In 2002, the WHO classification reduced the proportion of blasts in the bone marrow (BM) necessary for the diagnosis of acute myeloid leukemia (AML) from 30% to 20%, eliminating the RAEB-t subtype of myelodysplastic syndromes (MDS). However, this AML subtype, defined as low-blast count AML (LBC-AML, with 20–30% BM-blasts) is characterized by peculiar features, as increased frequency in elderly individuals and after cytotoxic treatment for a different primary disease (therapy-related), poor-risk cytogenetics, lower white blood cell counts, and less frequent mutations of NPM1 and FLT3 genes. The clinical course of this entity is often similar to MDS with 10–19% BM-blasts. The hypomethylating agents azacitidine and decitabine have been shown to induce responses and prolong survival both in MDS and LBC-AML. The role of these agents has also been demonstrated in AML with >30% BM-blasts, particularly in patients with poor-risk cytogenetics and in AML with myelodysplasia-related changes. Most recent studies are evaluating strategies to improve outcome, including combinations of hypomethylating agents with immune-response checkpoint inhibitors, which have a role in cancer immune surveillance. Efforts are also ongoing to identify mutations which may predict response and survival in these patients.