T-cell receptor αβ+ and CD19+ cell–depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency

Abstract

CD3TCRαβ and CD19 cell-depleted haploidentical or mMUD HSCT is a practical and viable alternative for children with a range of PIDs.

Different Phenotypic Presentations of X-Linked Lymphoproliferative Disease in Siblings with Identical Mutations

“…Active disease at HSCT, pre-transplant organ damage and use of a mismatched donor reduces post-HSCT survival to almost 50% [4]. With the improved outcomes associated with haploidentical HSCT in primary immunodeficiency [5], pre-emptive early HSCT could be considered for patients with XLP once stabilized after initial presentation even if a fully HLA-matched donor is not available.…”

RAG deficiency with ALPS features successfully treated with TCRαβ/CD19 cell depleted haploidentical stem cell transplant

“…CD34+ positive selection has advantages including low rates of graft-versus-host disease (GVHD) and high engraftment rate, but also has disadvantages, including slow immune reconstitution and increased risk of transplant-related mortality. Selective ex vivo depletion of TCRαβ cells and CD19+ B cells, preserving the TCRγδ and NK cell subsets in the graft, is a promising approach for treating both malignant and non-malignant disorders [7–9]. Regimens have not been standardized for patients with late onset combined immunodeficiency secondary to RAG deficiency [10].…”

Allogeneic CAR T cell therapies for leukemia

“…Broader experience from allo‐SCT, in particular haploidentical transplants, might inform dosing considerations in relation to thresholds for GVHD. Administration of >5 x 10 4 /kg haploidentical T cells is considered a threshold for increased likelihood of GVHD in pediatric allo‐SCT, and may provide a useful guide for the fully mismatched T cells. Unfortunately conventional strategies to mitigate against GVHD using systemic immunosuppression after infusion with agents such as Ciclosporin or Steroids are not readily applicable to the CAR setting where expansion, persistence and effector function are crucial.…”