Strategies to optimize the outcome of children given T-cell depleted HLA-haploidentical hematopoietic stem cell transplantation

Abstract

The most advanced frontier of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is represented by the use of an HLA-partially matched relative as donor. In this type of transplantation, donor-derived natural killer (NK) cells, which are alloreactive toward recipient cells, significantly contribute to the eradication of leukemia blasts. Alloreactive NK cells may also kill host dendritic cells and T lymphocytes, thus preventing graft-versus-host disease and graft rejection, respectively. Sophisticated strategies of adoptive infusion of T-cell lines/clones specific for the most life-threatening pathogens (namely cytomegalovirus, Epstein-Barr virus, Aspergillus and Adenovirus) have been envisaged, and successfully tested in a few pilot trials, to protect the recipient in the early post-transplantation period. In these patients, also ex-vivo expanded mesenchymal stromal cells have been shown to be beneficial for preventing graft failure. Novel and effective strategies aimed at further augmenting the graft-versus-leukemia effect and at optimizing prevention/treatment of opportunistic/viral infections are warranted.