Conditioning approaches in bone marrow transplantation. The cell target area and mechanism of cytotoxicity are major determinants of safety. Toxicity is a function of cell loss per se, the release of DAMPs from dying cells, and the introduction of mutations in cells that survive. DAMPs can drive unregulated immune responses and facilitate graft-versus-host disease (GVHD). Antigen-targeted mAbs that deliver cytotoxic but nongenotoxic payloads to specific cell types important for engraftment of donor cells after transplantation mitigate key safety concerns and have great potential for replacing X-irradiation and chemotherapeutic agents for bone marrow conditioning. Additional therapeutic antibody strategies, for example, targeting CD47 to enhance phagocytosis of HSCs, have also been described. HPC, hematopoietic progenitor cell. Professional illustration by Patrick Lane, ScEYEnce Studios.