Distinct Biomarker Profiles in Ex-vivo T cell depletion Graft Manipulation Strategies: CD34+ Selection vs CD3+/19+ Depletion in Matched Sibling Allogeneic Peripheral Blood Stem Cell Transplantation

Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft versus host disease (GVHD). However, direct comparisons between T-cell depletion strategies have not been well studied. We evaluated cellular and plasma biomarkers in two diff...

Full description

Saved in:
Bibliographic Details
Published in:Biology of blood and marrow transplantation 2017-11, Vol.24 (3), p.460-466
Main Authors: Cantilena, Caroline R., Ito, Sawa, Tian, Xin, Jain, Prachi, Chinian, Fariba, Anandi, Prathima, Keyvanfar, Keyvan, Draper, Debbie, Koklanaris, Eleftheria, Hauffe, Sara, Superata, Jeanine, Stroncek, David, Muranski, Pawel, Barrett, A. John, Battiwalla, Minoo
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft versus host disease (GVHD). However, direct comparisons between T-cell depletion strategies have not been well studied. We evaluated cellular and plasma biomarkers in two different graft manipulation strategies: CD3 + CD19 + cell depletion (CD3/19D) versus CD34 + selection (CD34S) and their association with clinical outcomes. Identical conditions including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source were used for each cohort. Major clinical outcomes were similar between the two groups in terms of overall survival, non-relapse mortality, and cumulative incidence of relapse, however, the cumulative incidence of acute GVHD trended to be higher in CD3/19D compared to CD34S. A distinct biomarker profile was noted in the CD3/19D cohort: higher levels of ST2, impaired Helios − FoxP3 + T regs reconstitution, and rapid reconstitution of naïve, Th2, and Th17 CD4 cells in the early post-transplant period. In vitro graft replication studies confirmed that CD3/19D disproportionately depleted T regs and other CD4 subset repertoires in the graft. This study confirmed the utility of biomarker monitoring which can be directly correlated to biological consequences and possible future therapeutic indications.
ISSN:1083-8791
1523-6536
DOI:10.1016/j.bbmt.2017.11.028