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There are patients affected by acute myeloid leukemia considered “difficult”. They are elderly or frail because they also have other diseases and therefore are not candidates for intensive chemotherapy, or they are patients in whom the standard therapy is not effective right from the start or loses effectiveness. For these people, it is urgent to find new therapeutic options, such as the combination of venetoclax (BCL 2 inhibitor) and a hypomethylating agent (azacitidine or decitabine).