Alpha/Beta T-Cell Depleted Grafts as an Immunological Booster to Treat Graft Failure after Hematopoietic Stem Cell Transplantation with HLA-Matched Related and Unrelated Donors

E Rådestad,M Uhlin,E Watz,M Engström,B Sundberg,H Wikell,S Thunberg,M Uzunel,J Mattsson

doi:10.1155/2014/578741

Abstract

Allogeneic hematopoietic stem cell transplantation is associated with several complications and risk factors, for example, graft versus host disease (GVHD), viral infections, relapse, and graft rejection. While high levels of CD3+ cells in grafts can contribute to GVHD, they also promote the graft versus leukemia (GVL) effect. Infusions of extra lymphocytes from the original stem cell donor can be used as a treatment after transplantation for relapse or poor immune reconstitution but also they increase the risk for GVHD. In peripheral blood, 95% of T-cells express the αβ T-cell receptor and the remaining T-cells express the γδ T-cell receptor. As αβ T-cells are the primary mediators of GVHD, depleting them from the graft should reduce this risk. In this pilot study, five patients transplanted with HLA-matched related and unrelated donors were treated with αβ T-cell depleted stem cell boosts. The majority of γδ T-cells in the grafts expressed Vδ2 and/or Vγ9. Most patients receiving αβ-depleted stem cell boosts increased their levels of white blood cells, platelets, and/or granulocytes 30 days after infusion. No signs of GVHD or other side effects were detected. A larger pool of patients with longer follow-up time is needed to confirm the data in this study.

Highlights

Today, allogeneic hematopoietic stem cell transplantation (HSCT) is commonly used as treatment for hematological malignancies, immunodeficiencies, and inborn errors of metabolism [1]
After allogeneic HSCT, increased frequency and function of γδ T-cells in transplanted patients are associated with a protective role against cytomegalovirus (CMV) reactivation and disease [23]
Cells obtained from apheresis from donors premobilized with granulocytecolony stimulating factor (G-CSF) (n = 4) or a buffy coat obtained from bone marrow (n = 1) were washed with CliniMACS buffer (Miltenyi Biotech) in a transfer bag by centrifugation at 200 g, 15 minutes with no brake at room temperature (RT)

Summary

Introduction

Allogeneic hematopoietic stem cell transplantation (HSCT) is commonly used as treatment for hematological malignancies, immunodeficiencies, and inborn errors of metabolism [1]. One solution has been positive magnetic enrichment of CD34+ HSCs from the graft, initially by Isolex 300i and later by the CliniMACS device [14,15,16,17] As this efficiently removes most CD3+ T-cells, thereby decreasing the risk of GVHD, patients are increasingly susceptible to relapse and infectious complications [18, 19]. After allogeneic HSCT, increased frequency and function of γδ T-cells in transplanted patients are associated with a protective role against cytomegalovirus (CMV) reactivation and disease [23] This is in line with other studies showing expansion and cytotoxic function of CMV-reactive γδ T-cells in the peripheral blood of patients receiving renal and lung transplants [24, 25]. The indication for infusion of αβ T-cell depleted graft in all patients was poor immune reconstitution associated with infectious complications

Material and Methods

Results

Discussion

Conflict of Interests