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Acute leukemia is a hematologic malignancy that affects people of all ages. Immunotherapies, including T-cell engagers, antibody-drug conjugates, and chimeric antigen receptor T-cell therapies have contributed to a paradigm shift in the treatment of patients with acute leukemia. Combined with advancements in allogeneic hematopoietic stem cell transplant and targeted therapy development, patients with acute leukemia have additional effective treatment options, providing the possibility of long-term remission. However, these advances have resulted in a complex and dynamic treatment landscape for clinicians to navigate. To guide the oncology community and provide a framework for patient care, the Society for Immunotherapy of Cancer convened a panel of experts to develop this clinical practice guideline on immunotherapy for the treatment of acute leukemia. Drawing from published data and clinical experience, the Expert Panel developed evidence-based and consensus-based recommendations relating to diagnostics; immunotherapies for the treatment of acute lymphoblastic leukemia, acute myeloid leukemia, and blastic plasmacytoid dendritic cell neoplasm; toxicity and safety management; treatment sequencing; and patient education and quality of life.