Early experiences with immune checkpoint blockade (ICB) in AML/MDS, such as durable remissions in post-transplant leukemia cutis relapse cases following CTLA-4 blockade (ipilimumab)84,85 or favorable associations of pretreatment T cell infiltration with clinical activity of PD-1 blockade (nivolumab) in combination with azacytidine86 generated a lot of interest to utilize ICB to address post-transplant and transplant-naïve AML relapse (Fig. 3). This evidence concerns the gene CTLA4 and acute myeloid leukemia.