Modern approaches to HLA-haploidentical blood or marrow transplantation

Abstract

HLA-haploidentical allogeneic blood or bone-marrow transplantation (haploBMT) has historically been associated with poor outcomes, owing to high rates of graft failure and graft-versus-host disease (GVHD) Several transplantation platforms have been developed that successfully overcome these historical barriers to haploBMT; three main approaches have been used extensively to conduct haploBMT procedures in patients T-cell depletion with 'megadose' CD34⁺ cells results in exceptionally low rates of GVHD, but is associated with poor T-cell function and thus high nonrelapse mortality (NRM), predominantly owing to infection The GIAC protocol, which involves in vivo modulation of T-cell-replete allografts, produces essentially universal engraftment with limited relapse and favourable survival, albeit with high rates of GVHD, particularly chronic GVHD Use of high-dose, post-transplantation cyclophosphamide after T-cell-replete allografting results in low rates of GVHD and NRM and favourable immune reconstitution, with somewhat higher rates of relapse, particularly after reduced-intensity conditioning No standard-of-care currently exists, as no completed prospective randomized studies have, thus far, compared any of these haploBMT approaches with each other or with transplantation approaches using other donor types