Title
TCRalpha/beta and CD19+ depleted Hematopoietic Stem Cell Transplant from Closely Matched Unrelated Donors or Haploidentical Related Donors for Hematologic Diseases and in Children and Young Adults

Description
This single institution, phase I clinical trial will determine the safety and feasibility of employing T-cell receptor (TCR) α beta+ and CD19+ (Cluster of Differentiation) depleted hematopoietic stem cell transplantation (HSCT) using peripheral blood stem cells (PBMC) from closely matched unrelated donors or haploidentical donors to treat non-malignant hematologic diseases in children and young adults. Allogeneic hematopoietic stem cell transplantation has become a curative option for children and adolescents with a variety of otherwise fatal conditions. To reduce the incidence and severity of graft-versus-host disease (GVHD) associated with allogeneic hematopoietic stem cell transplantation, donor grafts are depleted of T cells, either using CD34+ selection or CD3+/CD19+ depletion of grafts. However, these selection processes also deplete the graft of protective cell subsets, such as y delta T cells, natural killer (NK) cells, monocytes and dendritic cells, which play important roles in the immune response to infectious agents. Moreover, the presence of NK cells and y delta T cells in donor grafts is associated with more rapid immune reconstitution after HSCT transplantation. In order to retain these protective immune cell subsets, this trial will use a novel, highly selective graft engineering process using the Miltenyi CliniMACS system that selectively depletes y delta -T cells and B cells that are responsible for GVHD and Epstein Barr Virus (EBV)-related post-transplantation lymphoproliferative disorder, respectively. Prior to transplantation, patients will be treated with a conditioning regimen, specific for the original disorder.

Objective
The primary objective of this study is evaluation of the safety and feasibility of HSCT using TCRαβ+/CD19+ depleted hematopoietic stem cells to treat non-malignant hematologic diseases. This will be assessed by evaluating the incidence of graft failure, grade III-IV acute GVHD and chronic GVHD and TRM.

Secondary objectives include the evaluation of immune reconstitution and incidence of post-transplant infections, adverse events, serious adverse events, overall and disease-free survival and the efficiency of graft processing by the CliniMACS System.

Treatment This study is being done to see if the investigators can take peripheral blood stem cells from either an adult family member or a closely matched unrelated donor, and run them through a special lab instrument to remove alpha/beta T cells and B cells and then give them to the patient to treat disease. This is an experimental way of doing a hematopoietic stem cell transplant (HSCT). The investigators want to see if the new stem cells will grow without bad graft vs. host disease (GVHD). This treatment approach is experimental in the United States.

Key Eligibility For full eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Hematologic cancers, other

Participating Institutions
UW Health University Hospital