Haploidentical hematopoietic transplantation without T-cell depletion: current status and future perspectives

Human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (HLA-haplo HSCT) without T-cell depletion has tremendously progressed over the past 20 years and has become a feasible treatment option for leukemia patients without an HLA-identical sibling donor. Advances in conditioning regimens, graft manipulation, and pharmacological graft-versus-host disease (GVHD) prophylaxis have reduced the risk of fatal graft failure and severe GVHD, two of the most serious complications of traversing the HLA barrier. According to clinical observations, killer immunoglobulin-like receptor (KIR) mismatch and donor-specific anti-HLA (DSA) antibodies-negative status play potential roles in reducing the risk of GVHD and graft failure following HLA-haploidentical SCT. New strategies to improve transplant outcomes include donor lymphocyte, NK cell and selected T-cell subset infusion, mesenchymal stem cell (MSC) co-transplantation and interleukin-2 (IL-2) application. Future challenges remain in improving post-transplant immune reconstitution and finding the best approach to reduce the incidence and severity of GVHD while simultaneously preserving the graft-versus leukemia effect to prevent the recurrence of underlying malignancy.