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

• Main Authors: Emelie Rådestad, Mikael Sundin, Johan Törlén, Sarah Thunberg, Björn Önfelt, Per Ljungman, Emma Watz, Jonas Mattsson, Michael Uhlin
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-02-01
• Series: Frontiers in Immunology
• Subjects: αβ T-cell depletion; γδ T-cells; allogeneic hematopoietic stem cell transplantation; stem cell booster; donor lymphocyte infusion; graft manipulation
• Online Access: https://www.frontiersin.org/article/10.3389/fimmu.2019.00189/full

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.