New approaches to graft engineering for haploidentical bone marrow transplantation.

Haploidentical transplantation opens the possibility to offer this treatment to a large number of patients with an otherwise incurable disease, such as some hematologic or oncologic malignancies, inborn or acquired bone marrow failure syndromes, hemoglobinopathies, immunodeficiencies, or other genetic diseases. Initial attempts at haploidentical transplantation using unmanipulated bone marrow were associated with a high transplant-related mortality. However, recent insights into the biology of haploidentical transplantation, the availability of effective in vivo large-scale graft-manipulation technology, and improved supportive care strategies have led to and are still leading to significantly better outcomes compared to previous decades. Methods for the in vitro depletion of T lymphocytes from mobilized peripheral blood stem cells (PBSC) to prevent graft-versus-host disease (GvHD) have facilitated the wider use and acceptance of haploidentical transplantation in children and adult patients. Besides in vitro T-cell depletion techniques, other methods, such as the isolation of alloreactive natural killer (NK) cells, virus-specific T lymphocytes, and other effector or regulatory cells are nowadays available to rapidly rebuild the immune system after haploidentical transplantation for the prevention of severe infections or relapses of the underlying diseases.