Individualization of Hematopoietic Stem Cell Transplantation Using Alpha/Beta T-Cell Depletion

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with several potentially lethal complications. Higher levels of CD3+ T-cells in the graft have been associated with increased risk of graft-versus-host disease (GVHD), but also beneficial graft-versus-leukemia effect and reduced infections. To tackle post-transplant complications, donor lymphocyte infusions have been used but with an increased risk of GVHD. To reduce this risk, we performed depletion of αβ T-cells and treated 12 patients post-HSCT suffering from infections and/or poor immune reconstitution. The αβ T-cell depleted cell products were characterized by flow cytometry. The median log depletion of αβ T-cells was −4.3 and the median yield of γδ T-cells was 73.5%. The median CD34+ cell dose was 4.4 × 106/kg. All 12 patients were alive 3 months after infusion and after 1 year, two patients had died. No infusion-related side effects were reported and no severe acute GVHD (grade III-IV) developed in any patient post-infusion. Overall, 3 months after infusion 11 out of 12 patients had increased levels of platelets and/or granulocytes. In conclusion, we describe the use of αβ T-cell depleted products as stem cell boosters with encouraging results.

Impact of γδ T cells on clinical outcome of hematopoietic stem cell transplantation: systematic review and meta-analysis

“…Recently, ab T cell-depleted donor lymphocyte infusions to treat patients with poor immune reconstitution and infections were reported with encouraging results. 18 Eleven of 12 patients presented favorable responses with no increased risk of GVHD development, indicating that gd T-cell-enriched donor lymphocyte infusion products are a viable option to improve HSCT efficacy and safety after transplantation.…”

“…The successful use of ab T-cell-depleted cell products as stem cell boosters after HSCT in patients with poor graft function, primary graft failure, and/or infectious complications was recently reported. 18 CMV viremia is one of the most life-threatening infections after HSCT, being associated with high nonrelapse mortality in the first months posttransplant. Several works have reported a possible protective role of gd T cells on infections.…”

“…17 Altogether, these works propose that gd T cells might be beneficial in HSCT but with the cost of higher incidence of GVHD. Considering that ab T-/B-cell-depleted HSCT is increasingly used in patients with no matched donor [9][10][11] and that gd T cell-enriched donor lymphocyte products are being under current investigation, 18 consistent evidence is needed that supports beneficial effects of gd T cell enrichment with no detrimental effect to the patients. We aimed to determine whether the concentration of gd T cells in the graft or during immune reconstitution influenced the clinical outcome following HSCT and aGVHD incidence.…”

The Roles of γδ T Cells in Hematopoietic Stem Cell Transplantation

“…In this regard, the role of T cell subsets on GVHD has been extensively investigated. Several researchers reported that αβ T cells were considered to relate to the pathogenesis of GVHD, whereas γδ T cells receptor did not lead to GVHD and had strong antileukemia and antivirus activities 5 , 46 , 47 . Furthermore, γδ T cells were reported to play a protective role in GVHD, a heavy obstacle to the effectiveness of HSCT, as the cause of less risk of aGVHD in patients with higher γδ T cell concentration 8 .…”

Allogeneic Chimeric Antigen Receptor Therapy in Lymphoma

“…Developing CAR-T from a stem cell transplant donor αβ T cells are the main drivers of GvHD in allogeneic stem cell transplant recipients [24][25][26][27][28][29]. One strategy to decrease the risk of GvHD for patients who have already received an allogeneic stem cell transplantation and have subsequently relapsed is to derive CAR-Ts from the same donor T cells.…”