Ex vivo T-cell depletion in allogeneic hematopoietic stem cell transplant: past, present and future

Abstract

The most common cause of post-transplant mortality in patients with hematological malignancy is relapse, followed by GvHD, infections, organ toxicity and second malignancy. Immune-mediated complications such as GvHD continue to be challenging, yet amenable to control through manipulation of the T-cell compartment of the donor graft with subsequent immunomodulation after transplant. However, risk of both relapse and infection increase concomitantly with T-cell depletion (TCD) strategies that impair immune recovery. In this review, we discuss the clinical outcome of current and emerging strategies of TCD in allogeneic hematopoietic stem cell transplant that have developed during the modern transplantation era, focusing specifically on ex vivo strategies that target selected T-cell subsets.

Haploidentical transplantation in high‐risk pediatric leukemia: A retrospective comparative analysis on behalf of the Spanish working Group for bone marrow transplantation in children (GETMON) and the Spanish Grupo for hematopoietic transplantation (GETH)

“…It is necessary to optimize the protocols to prevent relapse, either by using more potent conditioning (with the risk of increasing TRM) using TBI, or by means of post‐transplantation target drugs and/or adoptive immunotherapy. This includes low‐risk alloreactive donor cell lymphocyte infusion, such as memory T cells, or NK cells that lack specific inhibitory receptors to enhance the graft vs tumor effect and decrease the risk of relapse . Along these lines, we are currently envisaging a new clinical trial using NK cell infusion early after haplo‐HSCT in children and adolescents with high‐risk hematological malignancies.…”

T‐cell receptor and B‐cell receptor repertoire profiling in adaptive immunity

“…However, mature donor cells can also attack the patient's organs due to antigen or HLA mismatches, leading to graft‐versus‐host disease (GVHD), a common cause of HSCT‐associated mortality. Thus, grafts are commonly depleted of mature T‐cells by ex vivo antibody (anti‐TCRα/β) capture or by chemical agents such as anti‐thymocyte globulin or cyclophosphamide . TCRβ repertoire evaluation has revealed lower diversity of both CD4+ and CD8+ subsets in recipients of T‐cell‐depleted grafts after 6 months compared to cord blood graft recipients .…”

Solid Tumor–Induced Immune Regulation Alters the GvHD/GvT Paradigm after Allogenic Bone Marrow Transplantation

“…However, this beneficial effect is often offset by GvHD, in which donor T cells attack normal host tissues (6). To attenuate GvHD, ex vivo T-cell depletion (TCD) of the allogenic bone marrow inoculum is typically applied, but unfortunately in hematologic malignancies, also results in a high rate of graft failure (7). Hence, the separation of GvT effects and GvHD remains an important research focus and the development of strategies to enable enhancing the GvT effects without GvHD is the ultimate goal of allo-BMT-based immune therapy.…”