TCR αβ+/CD19+ cell depletion in haploidentical hematopoietic allogeneic stem cell transplantation: a review of current data

Abstract

Allogeneic hematopoietic stem cell transplantation is a curative option for patients with a variety of diseases. Transplantation from a related haploidentical donor is being increasingly utilized for patients who lack an available human leukocyte antigen matched related or unrelated donor. One of the strategies used for haploidentical transplants involves selective depletion of T cells expressing the αβ T cell receptor and CD19+ B cells prior to transplant. This allows for the removal of cells responsible for graft-versus-host disease and post-transplant lymphoproliferative disorder but maintains hematopoietic progenitor and stem cells for engraftment (CD34+ cells), as well as cells to elicit graft-versus-tumor effect and provide anti-infective activity (such as gamma-delta T cells and natural killer cells). The aim of this review article is to present and discuss the data available to date from studies utilizing this method of transplantation.

Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients

“…Recently, the immunomagnetic depletion of TCRαβ + T- and CD19 + B cells cells has evolved to a fully automated and GMP-compliant operating procedure. Several single and multicenter retrospective studies already reported the safety and feasibility of TCRαβ/CD19 depletion as graft engineering approach [ 16 , 18 , 27 ].…”

Optimizing Blood Stem Cell Transplants Through Cellular Engineering

“…Thus, there is a need for research exploring how to maximize the anti-leukemic effects of the graft while removing the GvHD effect of transplanted cells 24 . One of the current methods for haploidentical transplantation is TCR αβ+/CD19+ cell depletion, in which there is a selective depletion of T cells expressing the αβ T cell receptor (TCR) and CD19+ B cells before transplantation, as these cells are responsible for GvHD [25][26][27] . However, T cells expressing γδ TCR are retained as γδ T cells are able to produce the GVT effect without causing GvHD 25,27 .…”

“…One of the current methods for haploidentical transplantation is TCR αβ+/CD19+ cell depletion, in which there is a selective depletion of T cells expressing the αβ T cell receptor (TCR) and CD19+ B cells before transplantation, as these cells are responsible for GvHD [25][26][27] . However, T cells expressing γδ TCR are retained as γδ T cells are able to produce the GVT effect without causing GvHD 25,27 . In one study, thirty-seven patients with primary immunodeficiency (PID) received transplants from a matched unrelated donor (MUD) or haploidentical mismatched related donor (MMRD), with all grafts being TCR αβ+/CD19+ depleted 28 .…”

<p>Role of Stem-Cell Transplantation in Leukemia Treatment</p>

“…65 In haploidentical transplantation, the graft contains lower of T-cell content to diminish GVHD. 66 Outcomes of haploidentical HSCT may be affected by innate immune cells like T cells and natural-killer cells. 67 In high-risk acute leukemia, the applicabilion of HLA-haploidentical HSCT is elevated.…”