title: A two-step approach to allogeneic haploidentical hematopoietic stem cell transplantation.
abstract: Strategies that exploit natural killer (NK) cell alloreactivity or attenuate rather than deplete T cells have resulted in improved outcomes after haploidentical hematopoietic stem cell transplantation (HSCT). However, no approach has consistently produced the triad of optimal immune reconstitution, avoidance of significant graft-versus-host disease (GVHD), and durable control of malignancy. We developed a two-step approach to haploidentical HSCT in which the lymphoid and myeloid portions of the graft are given in two separate steps in order to control and optimize T-cell dosing. The initial results from these trials have included robust immune reconstitution, low rates of toxicity and significant GVHD, and durable disease control in good-risk patients, as well as insights regarding a threshold for T-cell dosing above which graft-versus-tumor (GVT) effects might be expected. Patients who were not in remission at the time of HSCT had higher rates of relapse requiring efforts to further strengthen GVT effects. Second-generation trials are underway to further exploit changes in the dosing and timing of administration of T cells and to optimize donor selection in an effort to decrease relapse rates in high-risk patients.
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. dolores.grosso@jefferson.edu
authors.forename: Dolores
authors.initials: D
authors.lastname: Grosso
authors.forename: Neal
authors.initials: N
authors.lastname: Flomenberg
mesh_terms: D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous