Patient conditioning is a critical initial step in hematopoietic stem and progenitor cell (HSPC) transplantation procedures to enable marrow engraftment of infused cells. Conditioning regimens have traditionally been achieved by delivering cytotoxic doses of chemotherapeutic agents and radiation. However, these regimens are associated with significant morbidity and mortality, and cannot be used safely in elderly or subjects with comorbidities. Scientists at the National Heart, Lung, and Blood Institute (NHLBI), the University of Massachusetts Medical School (UMMS), and the University of Colorado (CU) have developed a recombinant bivalent (bi) single-chain variable fragment (scFV) minibody targeting the cMPL receptor on HSPCs, fused with diphtheria toxin (DT) truncated at residue 390 (DT390-biscFV(cMPL)) that can be used to deplete HSPCs with increased safety in patients undergoing HSPC transplantation.