Lymphoid reconstitution after autologous PBSC transplantation with FACS- sorted CD34+ hematopoietic progenitors

Catherine Bomberger, Meeta Singh-Jairam, Glenn Rodey, Anastasia Guerriero, Andrew M Yeager, William H. Fleming, H. Kent Holland, Edmund K. Waller

Research output: Contribution to journalArticle

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Abstract

T-cell and B-cell reconstitution was studied in nine patients who received fluorescence activated cell sorter (FACS)-sorted autologous CD34+ hematopoietic progenitor cells (HPC). The mean numbers of T cells (CD3+), B cells (CD19+) and CD34+ HPC administered to each patient were .004, .002, and 1.8 x 106 cells/kg, respectively. After high-dose myeloablative chemotherapy (busulfan, cyclophosphamide, etoposide) CD34+ HPC were infused and lymphoid reconstitution was monitored using flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of VDJ T-cell receptor (TcR) sequences. Restoration of normal numbers of peripheral blood T cells and B cells among recipients of FACS-sorted CD34+ HPC was delayed compared to recipients of non-T-cell-depleted PBSC autografts. In both patient groups, the circulating T cells were primarily CD4-, CD8+, αβ TcR+, and CD45RO+, CD45RA- during the first 2 months after transplant. Subsequent increases in the frequency of CD45RA+ CD45RO- T cells occurred at 2 to 3 months after transplant, suggesting maturation of CD34+ hematopoietic progenitors to 'naive' T cells. Analysis of the TcR repertoire after hematopoietic reconstitution demonstrated decreased diversity of Vβ TcR expression associated with global decreases in the absolute number of total peripheral blood T cells and most Vp TcR+ subsets. Three of nine recipients of FACS-sorted CD34+ HPC demonstrated significant increases in the percentage of γδ+ peripheral T cells and CD5+ B cells at 3 to 9 weeks after transplantation, and all patients had transient oligoclonal expansions of T cells expressing specific Vβ TcR. Transplantation with highly purified CD34+ HPC results in reduced diversity of the peripheral T-cell repertoire during the early post-transplant period compared with patients receiving unmanipulated or MoAb-depleted transplants.

Original languageEnglish (US)
Pages (from-to)2588-2600
Number of pages13
JournalBlood
Volume91
Issue number7
StatePublished - Apr 1 1998
Externally publishedYes

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T-cells
Autologous Transplantation
Fluorescence
T-Lymphocytes
Hematopoietic Stem Cells
T-Cell Antigen Receptor
Transplants
Cells
B-Lymphocytes
Blood Cells
Blood
Busulfan
Chemotherapy
Flow cytometry
Polymerase chain reaction
RNA-Directed DNA Polymerase
Cell Transplantation
Autografts
T-Lymphocyte Subsets
Etoposide

ASJC Scopus subject areas

  • Hematology

Cite this

Bomberger, C., Singh-Jairam, M., Rodey, G., Guerriero, A., Yeager, A. M., Fleming, W. H., ... Waller, E. K. (1998). Lymphoid reconstitution after autologous PBSC transplantation with FACS- sorted CD34+ hematopoietic progenitors. Blood, 91(7), 2588-2600.

Lymphoid reconstitution after autologous PBSC transplantation with FACS- sorted CD34+ hematopoietic progenitors. / Bomberger, Catherine; Singh-Jairam, Meeta; Rodey, Glenn; Guerriero, Anastasia; Yeager, Andrew M; Fleming, William H.; Holland, H. Kent; Waller, Edmund K.

In: Blood, Vol. 91, No. 7, 01.04.1998, p. 2588-2600.

Research output: Contribution to journalArticle

Bomberger, C, Singh-Jairam, M, Rodey, G, Guerriero, A, Yeager, AM, Fleming, WH, Holland, HK & Waller, EK 1998, 'Lymphoid reconstitution after autologous PBSC transplantation with FACS- sorted CD34+ hematopoietic progenitors', Blood, vol. 91, no. 7, pp. 2588-2600.
Bomberger C, Singh-Jairam M, Rodey G, Guerriero A, Yeager AM, Fleming WH et al. Lymphoid reconstitution after autologous PBSC transplantation with FACS- sorted CD34+ hematopoietic progenitors. Blood. 1998 Apr 1;91(7):2588-2600.
Bomberger, Catherine ; Singh-Jairam, Meeta ; Rodey, Glenn ; Guerriero, Anastasia ; Yeager, Andrew M ; Fleming, William H. ; Holland, H. Kent ; Waller, Edmund K. / Lymphoid reconstitution after autologous PBSC transplantation with FACS- sorted CD34+ hematopoietic progenitors. In: Blood. 1998 ; Vol. 91, No. 7. pp. 2588-2600.
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abstract = "T-cell and B-cell reconstitution was studied in nine patients who received fluorescence activated cell sorter (FACS)-sorted autologous CD34+ hematopoietic progenitor cells (HPC). The mean numbers of T cells (CD3+), B cells (CD19+) and CD34+ HPC administered to each patient were .004, .002, and 1.8 x 106 cells/kg, respectively. After high-dose myeloablative chemotherapy (busulfan, cyclophosphamide, etoposide) CD34+ HPC were infused and lymphoid reconstitution was monitored using flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of VDJ T-cell receptor (TcR) sequences. Restoration of normal numbers of peripheral blood T cells and B cells among recipients of FACS-sorted CD34+ HPC was delayed compared to recipients of non-T-cell-depleted PBSC autografts. In both patient groups, the circulating T cells were primarily CD4-, CD8+, αβ TcR+, and CD45RO+, CD45RA- during the first 2 months after transplant. Subsequent increases in the frequency of CD45RA+ CD45RO- T cells occurred at 2 to 3 months after transplant, suggesting maturation of CD34+ hematopoietic progenitors to 'naive' T cells. Analysis of the TcR repertoire after hematopoietic reconstitution demonstrated decreased diversity of Vβ TcR expression associated with global decreases in the absolute number of total peripheral blood T cells and most Vp TcR+ subsets. Three of nine recipients of FACS-sorted CD34+ HPC demonstrated significant increases in the percentage of γδ+ peripheral T cells and CD5+ B cells at 3 to 9 weeks after transplantation, and all patients had transient oligoclonal expansions of T cells expressing specific Vβ TcR. Transplantation with highly purified CD34+ HPC results in reduced diversity of the peripheral T-cell repertoire during the early post-transplant period compared with patients receiving unmanipulated or MoAb-depleted transplants.",
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