Three in a bed and changing allogeneic transplant outcomes with a second, non-engrafting cell source

Relapse remains the most significant cause of mortality after allogeneic transplant for leukemia despite advances in understanding of disease biology and newer, targeted treatment modalities. Cure after allogeneic transplant is mediated through the graft-vs-leukemia effect, as donor immune cells recognize and reject leukemic cells, largely through recognition of mismatched HLA and/or minor histocompatibility antigens. There is growing evidence that adjuvant but non-engrafting cellular therapies, either alone or in conjunction with conventional allogeneic transplant, improves leukemia outcomes and immune responses to such therapies have also been described during solid-organ transplants and following double cord unit transplantation, and are there associated with clinical consequences. We review these immune responses induced by third party and non-engrafting leukocytes and suggest possible mechanisms for the action of such cells. We further suggest that improved understanding of the nature of such responses might allow development of transplant technologies to make allogeneic transplants both better and safer, by targeting the immune response of the allogeneic immune system more specifically to leukemia.