In an interview conducted at the virtual European Hematology Association (EHA) Congress 2021, Andrew M. Brunner, MD, of Massachusetts General Hospital, Boston, Massachusetts, discusses the management of progression from myelodysplastic syndromes to acute myeloid leukemia, and he highlights the impact of receiving previous treatment with hypomethylating agents. He also discusses poor responses experienced by patients progressing to AML who received treatment with hypomethylating agents prior to receiving induction therapy. Finally, Dr Brunner provides alternative approaches.