The evolution of T‐cell depletion in haploidentical stem‐cell transplantation

Abstract

T-cell depletion (TCD) can prevent the onset of graft-versus-host disease (GvHD) in animal models of bone marrow transplantation; this manipulation enabled the successful application in the 1980s of T-cell depleted bone marrow (BM) for the treatment of babies with severe combined immune deficiency (SCID). However, in leukaemia patients, implementation of T-cell depletion has been more difficult, especially due to high rate of graft-rejection, leukaemia relapse and delayed immune reconstitution. These hurdles were gradually overcome by modifying the cell composition of the graft, and by reducing the toxicities associated with conditioning protocols. Although no 'gold standard' TCD method exists, T-cell depletion in its modern forms could offer clinical benefit, even for patients with a matched sibling donor.

Selective T‐cell depletion targeting CD45RA reduces viremia and enhances early T‐cell recovery compared with CD3‐targeted T‐cell depletion

“…T‐cell depletion (TCD) is important for haploidentical donor (haplo) hematopoietic cell transplantation (HCT) to reduce graft‐versus‐host disease (GVHD). TCD can be ex vivo in which T cells are removed from the allografts before infusion, or in vivo where anti‐lymphocyte antibodies or immunosuppressive drugs such as high‐dose cyclophosphamide are given to kill donor T cells after infusion . One early successful technique for haplo‐HCT gave an anti‐thymocyte globulin (ATG)‐containing preparative regimen with immunomagnetic enrichment of CD34+ cells .…”

“…TCD can be ex vivo in which T cells are removed from the allografts before infusion, or in vivo where anti-lymphocyte antibodies or immunosuppressive drugs such as high-dose cyclophosphamide are given to kill donor T cells after infusion. 1,2 One early successful technique for haplo-HCT gave an anti-thymocyte globulin (ATG)-containing preparative regimen with immunomagnetic enrichment of CD34+ cells. 3 This indirectly depleted T cells and other donor immune cells extensively.…”

Immune tolerance induction by nonmyeloablative haploidentical HSCT combining T-cell depletion and posttransplant cyclophosphamide

“…Over the past few years, the clinical use of haploidentical donors has gained great momentum, either through the use of megadose T-cell-depleted (TCD) peripheral blood progenitor cells (PBPCs) or unmanipulated transplants followed by high-dose posttransplant cyclophosphamide (PTCY). 1,2 The former approach is more time consuming and requires costly graft processing but offers better prevention of graft-versus-host disease (GVHD). Notably, although some risk of GVHD is tolerable in the treatment of patients with hematologic malignancies, this is unacceptable in the case of haploidentical transplantation for nonmalignant diseases.…”

Bone Marrow Homing and Engraftment Defects of Human Hematopoietic Stem and Progenitor Cells

“…Although the underlying mechanisms are not entirely known,53 it has been shown that residual host T cells with specific anti-donor or suppressive activity play a fundamental role, both in HLA matched and mismatched settings. Also, recipient natural killer (NK) cells are involved in the pathogenetic pathways leading to graft failure.…”