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

Frontiers in Immunology
E RådestadMichael Uhlin

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.

References

Jul 25, 1998·Bone Marrow Transplantation·M RembergerJ Aschan
Sep 9, 2009·British Journal of Haematology·Olle RingdénMichael Uhlin
May 19, 2010·Transplant International : Official Journal of the European Society for Organ Transplantation·Isabel Puig-PeyAlberto Sánchez-Fueyo
May 31, 2011·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Mats RembergerOlle Ringdén
Jan 26, 2013·Nature Reviews. Immunology·Pierre Vantourout, Adrian Hayday
May 28, 2014·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Alessandra StasiaAndrea Bacigalupo
Dec 3, 2014·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Ross PerkoMari H Dallas
Jun 9, 2015·The Journal of Clinical Investigation·Marie BleakleyWarren D Shlomchik
Jun 1, 2016·Frontiers in Immunology·Paola VaccaLorenzo Moretta
Oct 26, 2016·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Lia MinculescuHenrik Sengeloev

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Methods Mentioned

BETA
flow cytometry
density gradient centrifugation

Software Mentioned

FlowJo
Depletion
Prism
FACSDiva

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