Human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (HLA-haplo HSCT) without T-cell depletion has tremendously progressed over the past 20 years. Advances in graft manipulation

conditioning regimens

and pharmacological graft-versus-host disease (GVHD) prophylaxis have reduced the risk of fatal graft failure and severe GVHD. Donor-specific anti-HLA antibodies (DSA) negative status and killer immunoglobulin-like receptor (KIR) mismatch play potential roles in reducing the risk of graft failure and GVHD following HLA-haplo HSCT. New strategies to improve HLA-haplo HSCT outcomes include donor lymphocyte

selected T-cell subset and NK cell infusion

mesenchymal stem cell (MSC) co-transplantation and interleukin-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.