The history and future prospective of haplo-identical stem cell transplantation

Initial attempts at haplo-identical transplantation with T-cell replete bone marrow (BM) were associated with a high transplant-related mortality (TRM), mainly caused by severe graft-versus-host disease (GvHD), and previous efforts to prevent GvHD by ex vivo T-cell depletion of haplo-identical BM were associated with a high risk of graft failure and other complications. Improvements in large-scale T-cell depletion techniques of haplo-identical peripheral mobilized stem cells (PBSC) have overcome the human leukocyte antigen (HLA) barrier by using megadose numbers of stem cells obtained by either highly purified CD34(+) selection or negative depletion of T cells. In addition, recent insights into the role of graft-facilitating and anti-leukemic alloreactive natural killer (NK) cells, the permanent availability of the haplo-identical donor post-transplant and continuous improvements in graft-engineering techniques for the generation of effector cells for post-transplant adoptive transfer, have facilitated the development of strategies to decrease regimen-related toxicity through the use of less intensive preparative regimens, prevent severe infections by rebuilding the immune system and decrease the risk of relapse by exploiting the alloreactivity of donor NK cells and other donor-derived effector cells.