Advances in ex vivo T cell depletion - where do we stand?

Abstract

Graft-versus-host (GVHD) is an important cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). As donor T cells are recognized as key drivers of GVHD, some approaches to prevent GVHD have focused on T cell depletion of the allograft. In this review we summarize methods and outcomes of ex vivo T cell depleted (TCD) HCT with a focus on CD34+ selection. This platform is efficacious in preventing acute and chronic GVHD across a wide range of hematologic malignancies, and with the exception of chronic myeloid leukemia, is not associated with adverse relapse or survival outcomes compared to conventional GVHD prophylaxis platforms. In retrospective comparisons recipients of CD34+ selected HCT have higher rates of GVHD-free relapse-free survival (GRFS) than conventional HCT counterparts. Although CD34+ selected allografts require myeloablative and antithymocyte-globulin based conditioning to support engraftment, abrogation of calcineurin inhibitors and methotrexate in this approach reduces its toxicity such that it can be considered in select older and more comorbid patients who could benefit from ablative HCT. A trial comparing GVHD prophylaxis regimens (BMT CTN 1301, NCT 02345850) has completed accrual and will be the first to compare CD34+ selected HCT with conventional HCT in a randomized prospective setting. Its findings have potential to establish CD34+ selected HCT as a new standard-of-care platform for GVHD prevention.

A Phase I Study to Evaluate Two Doses of Wharton’s Jelly-Derived Mesenchymal Stromal Cells for the Treatment of De Novo High-Risk or Steroid-Refractory Acute Graft Versus Host Disease

“…The most effective approach to attenuate the risk and extent of aGVHD is to employ prophylactic strategies, the most common of which have included optimal major histocompatibility complex (MHC) Class I and II loci matching between donor and recipient; the pharmacologic blocking of T cell antigen recognition and resultant proliferation, principally through the employment of calcineurin inhibitors; in-vivo or ex vivo T cell depletion of the stem cell graft; or post-transplant cyclophosphamide [9][10][11][12]. Despite these measures, aGVHD remains a relatively common clinical challenge post Allo-HCT.…”