Immunomodulatory strategies for relapse after haploidentical hematopoietic stem cell transplantation in hematologic malignancy patients

Currently, human leukocyte antigen (HLA)-mismatched/haploidentical allografts have been validated as an alternative stem cell source for patients who have no immediate access to an HLA-matched related or unrelated donor. However, relapse remains a challenge after HLA-mismatched/haploidentical hematopoietic stem cell transplantation (HSCT) that is employed in the treatment of patients with hematological malignancies. In recent years, newly developed immunomodulatory strategies, which include prophylactic and therapeutic donor lymphocyte/natural killer (NK) cell infusion, donor selection based on NK alloreactivity/non-inherited maternal antigen (NIMA), immune reconstitution promotion, and application of exogenous cytokines, have made it possible to decrease the relapse rate and improve outcomes following haploidentical HSCT. Further elucidation of the underlying mechanisms that govern leukemia stem cell escape from immunosurveillance after haploidentical HSCT may broaden our understanding and lead to therapies that control relapse.