Allogeneic Hematopoietic Cell Transplantation and Cellular Therapy.

Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) generally require allogeneic hematopoietic cell transplantation (allo-HCT) for a cure, except for patients with favorable genetic genotypes such as those with core-binding factor AML. However, the use of intensive chemotherapy followed by prompt HCT does not fully prevent relapse or refractory disease. Despite improvements in transplant techniques and management of complications, further improvement of HCT outcomes is urgently needed. Moreover, careful patient counseling, donor selection, and choice of transplant type are essential to maximize the benefits of early allografting. Maintenance after HCT focusing on selective immunomodulation combined with targeted immunotherapies that control persisting or relapsed hematologic malignancies is currently under active investigation. To improve the balance between GVHD, relapse, and infection, the use of purified blood stem cell grafts in conjunction with expanded T-cells from stem cell donors targeting common infectious and leukemic antigens has been explored. T cells against infectious agents might also be generated using partially HLA-matched third-party T cells from cryopreserved cell banks, and a series of studies confirmed the clinical value of donor-derived CMV- and EBV-specific T cells. This approach has also been applied to acute leukemia, and trials using donor-derived cytotoxic T-cells targeting multiple leukemic antigens such as , , , and , as well as donor-derived CAR19 T-cells after allo-HCT, are currently underway.