This is a single center phase I/II clinical trial of CD16/IL-15/CD33 (161533) tri-specific killer cell engager (TriKE) for the treatment of CD33-expressing high risk myelodysplastic syndromes, refractory/relapsed acute myeloid leukemia or other CD33+ myeloid malignancies. The hypothesis is that 161533 TriKE will induce natural killer cell function by targeting malignant cells as well as CD33+ myeloid derived suppressor cells (MDSC) which contribute to tumor induced immunosuppression. Because CD16 is the most potent activating receptor on NK cells, this single agent may induce a targeted anti-CD33+ tumor response.