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T-cell reconstitution after unmanipulated, CD8-depleted or CD34-selected nonmyeloablative peripheral blood stem-cell transplantation

 

作者: Frédéric Baron,   Nicole Schaaf-Lafontaine,   Stéphanie Humblet-Baron,   Nathalie Meuris,   Emilie Castermans,   Etienne Baudoux,   Pascale Frère,   Vincent Bours,   Georges Fillet,   Yves Beguin,  

 

期刊: Transplantation  (OVID Available online 2003)
卷期: Volume 76, issue 12  

页码: 1705-1713

 

ISSN:0041-1337

 

年代: 2003

 

出版商: OVID

 

数据来源: OVID

 

摘要:

Background.We have previously shown that CD8 depletion or CD34 selection of peripheral blood stem cells (PBSC) reduced the incidence of acute graft-versus-host disease (GvHD) after nonmyeloablative stem-cell transplantation (NMSCT). In this study, we analyze the effect of CD8 depletion or CD34 selection of the graft on early T-cell reconstitution.Methods.Nonmyeloablative conditioning regimen consisted in 2 Gy total-body irradiation (TBI) alone, 2 Gy TBI and fludarabine, or cyclophosphamide and fludarabine. Patients 1 to 18 received unmanipulated PBSC, patients 19 to 29 CD8-depleted PBSC, and patients 30 to 35 CD34-selected PBSC.Results.T-cell counts, and particularly CD4+and CD4CD45RA+counts, remained low the first 6 months after nonmyeloablative stem-cell transplantation (NMSCT) in all patients. CD34 selection (P<0.0001) but not CD8 depletion of PBSC significantly decreased T-cell chimerism. Donor T-cell count was similar in unmanipulated compared with CD8-depleted PBSC recipients but was significantly lower in CD34-selected PBSC recipients (P=0.0012). T cells of recipient origin remained stable over time in unmanipulated and CD8-depleted PBSC patients but expanded in some CD34-selected PBSC recipients between day 28 and 100 after transplant. Moreover, whereas CD8 depletion only decreased CD8+counts (P<0.047), CD34 selection reduced CD3+(P<0.001), CD8+(P<0.016), CD4+(P<0.001), and CD4+CD45RA+(P<0.001) cell counts. T-cell repertoire was restricted in all patients on day 100 after hematopoietic stem-cell transplantation but was even more limited after CD34 selection (P=0.002).Conclusions.Despite of the persistence of a significant number of T cells of recipient origin, T-cell counts were low the first 6 months after NMSCT. Moreover, contrary with CD8 depletion of the graft that only affects CD8+lymphocyte counts, CD34 selection dramatically decreased both CD8 and CD4 counts.

 

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