Donor selection, graft engineering, and dosing oh my!

Allogeneic hematopoietic cell transplantation is a potentially curative therapy for patients with both malignant and nonmalignant disorders. To select the optimal donor for allogeneic hematopoietic cell transplantation, the first step is to search for a matched sibling donor or a matched unrelated donor, both of which yield comparable outcomes in the current clinical landscape. Additional donor options include haploidentical donors, mismatched unrelated donors, and umbilical cord blood donors. Newer transplant approaches have refined the use of these donor sources to improve outcomes. Beyond human leukocyte antigen compatibility, several non-human leukocyte antigen factors influence optimal donor selection. These include donor age, the presence of donor-specific antibodies, cytomegalovirus status, and ABO blood type compatibility. Various graft engineering strategies have been developed. These include posttransplant cyclophosphamide, T-cell depletion techniques such as CD34+ selection, CD45RA depletion, and αβ T-cell depletion, T regulatory purification, and umbilical cord blood expansion. Optimizing the cell dose used in transplantation is also critical to improving outcomes. All of these strategies combined allow nearly every patient to find a donor with continued improvements in outcomes.