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

Front Immunol. 2019 Feb 11:10:189. doi: 10.3389/fimmu.2019.00189. eCollection 2019.

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.

Keywords: CliniMACS; allogeneic hematopoietic stem cell transplantation; donor lymphocyte infusion; graft manipulation; stem cell booster; αβ T-cell depletion; γδ T-cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers
  • Bone Marrow Cells / metabolism
  • Child
  • Child, Preschool
  • Female
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / methods
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Immunophenotyping
  • Infections / etiology
  • Leukocyte Count
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Depletion* / methods
  • Male
  • Middle Aged
  • Precision Medicine* / methods
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*
  • Retrospective Studies
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • Transplantation, Homologous
  • Young Adult

Substances

  • Biomarkers
  • Receptors, Antigen, T-Cell, alpha-beta